Intermediate Filaments And Cell Signalling

Front 1

Intermediate Filaments

Back 1

-Non polar

-2 parallel monomers coiled to make dimer

-2 staggered anti-parallel dimers make tetramer

-Link tetramers end to end

-Forms rope

Front 2

Types of Intermediate Filaments

Back 2

Keratin
Filamentin
Nuclear Lamins
Neurofilaments

Front 3

Keratins

Back 3

Have multiple isoforms

expressed in epitehlia

form hard tissues like hair and nails

Front 4

Hyperkeratinosis

Back 4

too much keratin, cells can rupture under minor stress

blistering caused by minor trauma

Front 5

Vimentin

Back 5

mesenchymal cells, blood vessel endothelium, and some epithelia

Terminate at nuclear membrane and cell surface desmosomes

maintain cell organization

reorganized in mitosis

associate with MTs by accessory proteins

HOLDS NUCLEUS IN RIGHT POSITION

Front 6

Neurofilaments

Back 6

fills core of axons
associate with MTs
control radial growth and diameter of axon and thus the SPEED OF CONDUCTION

Front 7

Nuclear Lamina function

Back 7

supports nuclear membrane, attached to inner surface of nuclear membrane

Front 8

Lamin Types

Back 8

A and C spliced products of same gene

B: encoded by its own gene, remodeled in mitosis

Phosphorylation by a kinase causes depolymerization

Front 9

Intermediate FIlament Associated proteins

Back 9

Either cross links IF to another IF or another structure

No molecular motors are used for IFs

Front 10

Microtubule Based Structures

Back 10

CIlia, Flagella, Mitotic Spindle

Front 11

Alpha/Beta tubulin Dimers

Back 11

Building blocks of MTs

Bind GTP (alpha is never hydrolyzed, beta is)

Alpha end: minus end

Beta End: plus end

Elongation occurs at beta end

13 filaments form tubule

Front 12

MT dynamics

Back 12

GTPase activity of dimers hydrolyzes GTP to GDP

GDP-tubulin is unstable and the tubule falls apart

Can have glycines on exterior (no charge) or glutmates (strong negative charge)

Front 13

Colchicine

Back 13

Prevents mitotic spindle formation

causes depolymerization

Treats gout, used to treat cancer

Front 14

Nocodazole

Back 14

Not used in medicine, MT depolymerizer

Front 15

Taxol

Back 15

prevents MT disassembly

Front 16

MT nucleation

Back 16

1) come from triplet MTs of centriole (or doublet in cilia and flagella)

2)gamma tubulin ring in pericentriolar material of centrosome

Front 17

MT polarity

Back 17

+ end goes to membrane

- End goes to nucleus

Front 18

Microtubule Associated Proteins

Back 18

Stability and assembly factors

Define inter-MT spacing

Front 19

TAU

Back 19

MAP, present in axons, either the cause of or a symptom of Alzheimers

Front 20

Ending Binding Proteins

Back 20

MAPs that bind the plus ends of MT

prevent elongation

Front 21

Actin arrays

Back 21

Cortical Array (maintain cell shape)

Lamellipodia (cell movement)

Bundles (scaffold for cell extension)

Meshworks

Stress Fibers (connect adhesion plaques)

Muscle thin filaments

Cyotkinetic contractile ring

Front 22

Actin Monomer

Back 22

Use ATP

ATPase activity

Must have ATP bound to polymerize

Barbed (plus ends)

Arrow/pointed (minus ends

Front 23

Actin polymerization

Back 23

-Stable seed: 3 actin monomers (3rd order)

-Actin added to both ends

Front 24

Critical concentration

Back 24

concentration of actin needed fro polymerization to occur

+ and - ends have different Cc

Front 25

Treadmilling

Back 25

Concentration is in between Cc of + and - Ends

Adding MT on the plus end, While taking them off on the minus end

Front 26

Cytochalasins

Back 26

Caps plus end of actin, minus end slowly depolymerizes

Front 27

Phalloidin

Back 27

Cap both ends of actin, no depolymerization is possible

Front 28

Actin-Binding Proteins

Back 28

Some bind actin to lower the free concentration causing less polymerization

can also release to increase actin concentration to cause polymerization

some severe proteins

some severe and cap end

some cause networking

Front 29

Actin related proteins

Back 29

bind to side of actin filament

causes branching!

Front 30

Small GTPase activity in cytoskeleton

Back 30

CDC42: filopodia

RAC: cortial

Rho: stress fibers anchored to cell-substrate adhesion plaques

GTPase causes which actin array it creates

Front 31

Myosin action

Back 31

2 Heads acting indepdently

bind ATP, hydrolyze ATP (PO4 of light chain)

Now binds to Actin Filament

Phosphate realease, head moves the filament

ADP released, ATP Binds, release filament, hydrolyze ATP, Recock the head

Move towards plus end

Front 32

Kinesin Action

Back 32

ADP bound, one head binds MT, ADP released

ATP binds, neck linker binds to catalytic core

2nd head thrown foward to the next site

trailing head hydrolyzes ATP

leading head exchanges ADP for ATP binds

trailing head moves forward

Front 33

Polarity of Kinesin Family Motors

Back 33

N terminal: + end director

C-Terminal: - end director

Internal Motor: MT depolymerizing activity

Front 34

Calcium regulation of muscle contraction

Back 34

Released from SR by stimulus from nervous system

binds troponin which moves tropomyosin which allows myosin head to bind actin

Front 35

Dyenin Functions

Back 35

CIliary/Flagella motility and left/right asymmetry

cytoplasmic dynein: mitosis, nuclear envelope breakfown, vesicle transport, golgi maintence, viral transport

DYENIN IS MINUS END DIRECTOR

Front 36

Dynactin complex

Back 36

Small ARB protein and another protein link dynenin to the microtubule

ADAPTER PROTEIN

Front 37

4 Types of cilia

Back 37

Motile 9+2 (sperm, trachea, oviducts)

Motile 9+0 (nodal cilia)

Immotile 9+2 (kinocilium in the ear, Sensory)

Immotile 9+0 (cells in G0, sensory)

Front 38

Embryogenesis and monocilia

Back 38

Motile 9+0 monocilia create flow during embryogenesis that causes an uneven dristribution of hedgehog protein which causes the polarity of cells to form.

Front 39

Smooth ER

Back 39

Synthesizes lipids

modifies lipid soluble chemicals (cytochrome p450) to be secreted in urine

Front 40

Signal recognition paritcle

Back 40

Binds the polypeptide as it is synthesized, stops translation

binds the SRP receptor on ER and is removed

Front 41

Transmembrane Domain creation

Back 41

the mRNA encodes an internal sequence that stops transfer through the ER Membrane

another sequences can start the transfer again to make another TM domain

Front 42

Where does Glycosylation occur?

Back 42

Asparagine residues. The carbs are ended in the ER post translationally

Front 43

Vesicle pathways

Back 43

Move from ER to golgi

Can then be sent to either PM, Late endosomes (which become lysosomes for degradration) or secreted out into the cell

Front 44

Vesiscle budding

Back 44

Cargo receptor in membrane binds cargo, adaptin links to the cargo receptor on other side, clathitin binds to adaptin, budding occurs

Front 45

Vesicle Docking

Back 45

t Snare on desired compartment

v Snare on vesicle

snares bind eachother and wrap around eachother causing lipids from the membranes to leak into eachother and the vesicle to be incorporated into each other

Front 46

Golgi body structure

Back 46

Flattened sacs that each are slightly different and different modifications occur in each sac

Front 47

Lysosome Structure

Back 47

H-Atpase imports H ions into the lysosome to lower the pH and activate all the -ases in the lysosome

Metabolite transporters allow for the degraded products to be removed from the cell

Front 48

Clatharin Protein

Back 48

activated when GTP is bound, has inherent GTPase activity, release the vesicle when GTP is hydrolyzed to GDP

Front 49

LDL endocytosis

Back 49

LDL binds receptor EC, clatharin coated vesicle, fusion with late endosome, degradation of lipoproteins with conservation and recycling of the receptor

Front 50

Channel Types

Back 50

Voltage gated: activated by polarization

Stress: activated by stretch

Ligand: activated by agonists or antagonist molecules

Front 51

P-type Atpase

Back 51

catalyze auto-phosphorylation

Front 52

V-type ATPase

Back 52

Catalyze ATP hydrolysis

Front 53

Nernst Equation

Back 53

Ex= -61 /Zx * Log ([Xi]/[Xo])

Front 54

Hypotonic

Back 54

Cell swells

osmolarity inside cell is greater than the osmolarity outside the cell

Front 55

Hypertonic

Back 55

Cell shrinks

osmolarity inside the cell is less than the osmolarity outside the cell

Front 56

Isotonic

Back 56

cell stays same size

osmolarity inside and outside the cell is equal

Front 57

Effective Osmolality

Back 57

it a solute is permeable to the membrane, the osmotic force is lowered

Front 58

effective osmolality equation

Back 58

π=(Sigma)(nCRT)

0<sigma<1

-if sigma is 0, it can cross the membrane

-if sigma is 1, it CANNOT cross the membrane

Front 59

Oncotic Pressure

Back 59

movement of fluid betweendinterstitial fluid and plasma

oncotic pressure graph isn't linear

Front 60

osmotic pressure

Back 60

movement of fluid between extracellular fluid and intracellular fluid

graph is linear

Front 61

Body Fluid Breakdown

Back 61

2/3 is ICF

1/3 is ECF

25% of ECF is Plasma

75% of ECF is interstitial fluid

Front 62

Na/K ATPase

Back 62

3 sodium out, 2 potassium in

creates negative charge on inside of cell

slow leak of potassium out of cell

Front 63

Potassium

Back 63

High IC

Low EC

Front 64

Sodium

Back 64

High EC

Low IC

Front 65

Chloride

Back 65

High EC, moves out via channels

negative charge on chloride ion is important

Front 66

Secondary Active transport

Back 66

Uses energy stored in sodium gradient built by Na/K ATPase

Energy is used for glucose symporter into the cell and for hydrogen antiporter (pumps H ion out of the cell)

Front 67

Functions of Epithelia

Back 67

Barrier to movement

vectorial transport (crossing the epithelium)

modification of environment (secretion and absoption)

Sensory

Conveyence (move substances along epithelium, cillia)

Front 68

Characteristics of Epithelia

Back 68

Avascular

densely cellular

polarized

mitogenic

separated from/attached to connective tissue by basal lamina

Front 69

Polarity of Plasma membrane in epithelial cells

Back 69

Plasma membrane in apical surface difference in composition and function from basal plasma membrane

Front 70

Polarity of Organelles in epithelial cells

Back 70

Mitochondria in basal portion of kidney tubule (ATP needed for sodium potassium pump)

golgi body in apical surface (secretion of proteins)

Front 71

Mitogenic properties of Epithelia

Back 71

Small intestine: mitosis occurs in crypts then grows to the top of the villi and is shed

Front 72

Epithelial Specializations

Back 72

Adhesion and communication

increased surface area (absorption)

Motility

Protection (keratinization)

Front 73

Cadherins

Back 73

Adhesive proteins

homophilic interaction

require calcium binding to function

Front 74

IG Superfamily

Back 74

Adhesive proteins, homophilic, similar to antibodies in structure

Front 75

Selectins

Back 75

adhesive proteins, bind carbs to mediate connection with ECM

Heterophillic

Front 76

Integins

Back 76

heterophillic

bind fibronectin

Front 77

Zonula Adherens

Back 77

transmembrane adhesive proteins: E-Cadherin and Nectin

Cytoplasmic linker proteins: alpha and beta catentin

Cytoskeletal fragments: Actin

Front 78

Beta-Catenin

Back 78

When cadherein is bound to something else, beta-catenin is bound to cadherin

when cadherin is not bound, beta-catenin dissociates and is either degraded or activates transcription factors

Front 79

Neoplasia characteristics

Back 79

no differentiation or maturation, lack of polarity, big nuclei, prominent nucleoli

Front 80

Desmosomes

Back 80

connect cells that are side by side

TM protein: desmogleins and desmocollins(cadherins)

Linkers: catenins (desmoplakin and plakoglobin)

Cytoskeletal filaments: (cytokeratins)

Front 81

Hemidemosomes

Back 81

attach epithelial cells to the ECM

TM proteins: integrins and type 17 collagen

Linkers: Plectin and BP230

Cytoskeletalfilaments: cytokeratins (IFs)

Front 82

Focal Contacts

Back 82

TM protein: integrins

Linker: talin, paxillin, vinculin, actinin

cytoskeletal filaments: actin

link cytoskeleton to ECM

role in cell migration

signalling: Focal adhesion kinase

Front 83

Tight Junctions

Back 83

encircle cell a cell at apical lateral intercellular space

regulate paracellular activity with selective transport

maintain cell polarity

Front 84

Tight junction components

Back 84

cytoskeleton: actin

TM: claudins

cytoplasmic proteins: g proteins, kinases, TFs, polarity complexes, cingulin

Front 85

Gap junctions

Back 85

allow metabolic and electrical coupling between cells

communication via small molecules (less than 1000 daltons)

Front 86

Gap junction components

Back 86

Connexins are TM proteins

6 come together to form connexons

connexon is gated and regulated

Front 87

Basal lamina components

Back 87

laminin, type 4 collagen, nidogen, heparan sulfate proteoglycan

Front 88

Basal lamina functions

Back 88

attaches epithelium to connective tissue

substrate for cell migration

barrier to passage of cells

selective filtration barrier (kidney)

Front 89

Microvilli

Back 89

increase SA

core of actin filaments

actin binding and bundling proteins important

Front 90

Cilia

Back 90

motile (9+2)

Immotile (sensory, 9+0)

grow from the basal body

Front 91

Keratinization

Back 91

protection

variable thickness

accumulation of IF cytokeratins

dead cells are shed at surface

Front 92

Simple columnar epithelial cells example

Back 92

small intestine (ileum)

Front 93

Simple cuboidal epithelium example

Back 93

collecting duct in the kidney

Front 94

Stratified squamous example

Back 94

esophagus

Front 95

stratified cuboidal example

Back 95

sweat gland DUCT

Front 96

Psuedo Stratified columnar example

Back 96

looks stratified but it isn't really

trachea

Front 97

transitional epithelium

Back 97

in the bladder, highly impermeable

dome cells (aka umbrella cells) cover the cells below

less layers of cells allow for stretch in BLADDER

Front 98

Exocrine Glands

Back 98

have ducts

polarized, product released apically

products act locally (surface or lumen)

Front 99

Endocrine glands

Back 99

lose connection with surface epithelium

no obvious polarity, release products into EC space

products circulated in vasculature

Front 100

Simple squamous cell example

Back 100

bowman's capsule

Front 101

Exocrine complexity characteristics

Back 101

unicellular or multicellular

branched or unbranched

tubular or acinar (spherical)

Front 102

Types of exocrine cells/secretions

Back 102

mucous (High MW glycoproteins)

serous (proteins, glycoproteins, enzymes)

mixed (cells of both types)

Front 103

Manner of Exocrine product realease

Back 103

merocrine (exocytosis)

apocrine (part of apical cytoplasm lost in secretion)

holocrine (cell dies as product is released, whole cell secreted)

Front 104

Goblet cells

Back 104

unicellular glands that secrete mucous

Front 105

Myoepithelial cells

Back 105

contracile (move secretion to gland opening)

maintain cell polarity

produce tumor supressor factors

found in sweat, mammary, and salivary glands

Front 106

Polypeptide secreting endocrine glands

Back 106

pituitary, pancreas, parathyroid

Front 107

steroid secreting endocrine glands

Back 107

adrenal cortex, gonads

Front 108

modified amine secreting endocrine glands

Back 108

adrenal medulla, thyroid

Front 109

Epithelial Cell regulatory functions

Back 109

1) volume of body fluids (sodium/water balance)

2)composition of body fluids (organic and inorganic solutes)

3) temperature

Front 110

ADH

Back 110

-Secreted by hypothalamus

-protein hormone

-binds basolaterally and works via cAMP into aquaporins stored in vesicles into the luminal side

-water flows into the cell due to the increased osmolarity

Front 111

Aldosterone

Back 111

Activated by low salt dieting (or sweating a lot for a long period of time)

steroid hormone

IC receptor, binds and causes more sodium channels to be put in the apical membrane, enhancing absorption of sodium chloride and thus water (it follows the concentration gradient)

Front 112

Routes Through cells

Back 112

Paracellular: around the cell (Chloride)

Transcellular: anything other than small, nonpolar molecules require a channel of some type

Front 113

Sodium Potassium Pump

Back 113

3 sodium out, 2 potassium in

makes the cell negatively charges

requires ATP

potassium also leaks out of the cell

Front 114

Chloride transport

Back 114

Chloride is negative

Sodium moved across membrane (transcellularly) via channels

this makes the lumen negative

chloride tries to move away from the negatively charged lumen and moves paracellularly (around the cells)

Front 115

Changes in the membrane potential

Back 115

big changes occur by the movement of very few ions (the balance is fragile)

Front 116

Functions of connective tissue

Back 116

immune function

developement and signallng

tensile strength and flexibility

structural support and cushioning

nutrition supply and waste removal

adhesion

Front 117

Loose connective tissue characteristics

Back 117

cellular, abundant ground substance, collagen fibers are sparse and thin

beneath the epithelia, sorround blood vessels and ducts

Front 118

dense irregular connective tissue characteristics

Back 118

collagen bundles, not uniformly oriented (can resist stretch in several directions)

few cells

less ground substance

dermis, intestinal mucosa

Front 119

Dense regular connective tissue

Back 119

collagen fiber bundles are parallel

little ground substance

fibroblasts aligned between bundles

ligaments and tendons

Front 120

Reticular Fibers

Back 120

type 3 collagen

branched and thin

highly glycosylated

support stromal (connective tissue portion of a tissue) framework

hematopoietic and lymphatic tissues

Front 121

Mesenchyme Facts

Back 121

present mainly in embryonic stage

forms fat, cartilage, muscle, and bone

composed of irregular cells embedded in jelly-like matrix with fine fibers

source of all other connective tissues

Front 122

Type 1 collagen

Back 122

2 alpha-1 (I) and 1 alpha-2 (I) helix

fibrillar

skin, bone, tendon

resist tension and stretch

Front 123

type 2 collagen

Back 123

3 alpha-1 (II)helices

fibrillar

cartilage

resists intermitten pressure

Front 124

type 3 collagen

Back 124

3 alpha-1(III) helices

fibrillar

organs and blood vessels

loose meshwork of reticular fibers

Front 125

type 4 collagen

Back 125

2 alpha-1(IV) and 1 alpha-2 (IV) helices

basement membrane

support and filtration

Front 126

Collagen alpha chain characteristics

Back 126

Glycine-Proline-Hydroxyproline repeats common

Glycine has no side chain, increasing flexibility of helix

Front 127

Collagen biosynthesis

Back 127

translated across rER membrane while being glycosylated

the 3 pro-alpha helices self assemble to make pro-collagen which is then secreted

once secreted, the propeptide signals are cleaved to form collagen (by endopeptidases)

(they were left on to prevent spontaneous linkage of collagen which occurs EC)

Front 128

Prolyl hydroxylase

Back 128

hydroxylates proline,

requires ascorbic acid,

ascorbic acid deficency causes scurvy (slow wound healing and causes joint issues)

Front 129

Structure of Collagen fibrils

Back 129

They are staggered and NOT linked head to tail but instead CROSSLINKED to the fibril on top of them

this is done by the enzyme LYSYL OXIDASE

which links lysines to hydroxlysines (also occurs in elastin)

Front 130

Osteogenesis Imperfecta

Back 130

Type 1: halpoinsufficency, make less collagen but it is function, mild condition (insufficient col1a1)

type 2: dominant negative mutation, collagen is abundant but structurally abnormal and not functional (due to mutated col1a1)

Front 131

Ehlers-Danlos Syndrome

Back 131

variable mutation of collagen genes and collagen processing genes

causes vascular defects, fragile and hyperextensible skin, and joint hypermobility

Front 132

Elastin

Back 132

forms rubber-like fibers

rich in proline, glycine, valine, and other hydrophobic AAs

lysine base crosslinks

little hydroxyproline

Front 133

Marfan Syndrome

Back 133

mutation in fibrillin-1 gene, can't sequester growth factors TGF-beta and BMP

occular, musculoskeletal, cardiovasular defects,

aortic aneurysm

Front 134

Ground substance components

Back 134

glycosaminoglycans

proteoglycans

adhesive glycoproteins

(these are ECM macromolecules)

Front 135

glycosaminoglycans

Back 135

long unbranched polysacchride (composed of repeating disaccharides)

very negative charge (due to sulfate and carboxyl groups located on many of the sugars) this attracts Na+ and H20, forming a hydrated gel (The gel like composition of ground substances permits rapid diffusion of water-soluble molecules.)

usually are secreted from the cell as a post-transcriptional modification of proteins called proteoglycans (with the exception of Hyaluronic acid/Hyluronan)

Front 136

Proteoglycans?

Back 136

composed of a core protein and a GAG

up to 95% is a carbohydrate

very big and negatively charged

resist compression when hydrated

bind growth factors

Front 137

Aggrecan

Back 137

proteoglycan found in cartilege

contains keratin sulfate and chondrotin sulfate

Front 138

Syndecans

Back 138

proteoglycan that target cells to their correct location during embryogenesis

Front 139

Hyaluronan/Hyaluronic Acid

Back 139

Special GAG that does NOT form proteogylcans

Large, free carbohydrate chain

proteoglycans actually bind to hyaluronan via LINK PROTEINS forming giant macromolecules called PROTEOGLYCAN AGGREGATES

(which are abundant in the ground substance of cartilage, allowing for resistance of compression and flexibility (excellent shock absorbers))

Front 140

Multi-adhesive glycoproteins

Back 140

link cells and ECM molecules

examples: fibronectin, tenascin, and laminin

binds at the RGD sequence (arginine-glycine-aspartic acid)

Front 141

FIbronectin

Back 141

multi-adhesive glycoprotein that binds collagen

Front 142

Integrins

Back 142

receptor on plasma membrane

bind ECM molecules at RGD sequence

IC domain of receptor links with actin filaments via adapter protein

Front 143

Integrin signalling

Back 143

inside-out: signals from cytoskeleton can activate the receptor to bind ECM molecules

Outside in: singals from ECM can cause the IC domain to bind cytoskeleton which results in growth, survival, and differentiation

Front 144

Collagenases

Back 144

Clip one spot on collagen fibril, denaturing the helix, allowing other enzymes to degrade the collagen

Front 145

Functions of Matrix Metalloproteinases

Back 145

ECM remodeling

Bone remodeling

vascular development and angiogenesis

regulation fo cell migration

modulation of growth factors and cytokines

cellular invasion and metastasis

Front 146

Fibroblasts

Back 146

synthesizes collagen and the ECM

Front 147

myofibroblasts

Back 147

activated following tissue injury (induced by TGFbeta)

express smooth muscle actin and non-muscle myosin which and contract and close wounds

then they magically disappear after the wound heals

Front 148

Pericyte

Back 148

multipotent stem cells

located in perivascular area in microvasculature

Front 149

Mast Cells

Back 149

Release histamine, proteoglycans, and heparin

activated by antigens (allergies)

Front 150

Plasma cells

Back 150

Terminally differentiated B cell

make and release 1 single type of antibody

Front 151

Macrophage

Back 151

Engulfs pathogens (phagocytosis)

derived from monocytes

process antigens

Front 152

White adipose tissue

Back 152

stores fat for use by body in fast or in medium intensity exercise

Front 153

Brown Adipose tissue

Back 153

there is no coupling between electron transport and the ATP synthase channel

releases all energy as heat (important in babies)

Front 154

Retrotransposons

Back 154

work like retroviruses, add themselves to our DNA via RNA intermediates

1.5 million copies in the genome

Front 155

RNA Facts

Back 155

Transcribed and translated in the 5' to 3' direction

uracil replaces thymidine

requries no primer to start synthesis

Front 156

RNA Polymerase 1

Back 156

transcribed most rRNA genes

Front 157

RNA polymerase 2

Back 157

transcribes most mRNAs and miRNAs, and some small RNAs

Front 158

RNA polymerase 3

Back 158

transcribes tRNA genes, 5s rRNA genes, and many other small RNAs

Front 159

Eukaryotic promoter elements

Back 159

Bre: -35

TATA: -30

INR: Transcription start point (+1)

DPE: +30

Front 160

Eukaryotic transcription factors

Back 160

Bind the DNA, then the RNA polymerase binds

They contain arginine residues which hydrogen bond with thymidine and adenine

this occurs in major groove of the DNA

Front 161

Enhancer Elements

Back 161

DNA sequences that can be far away from the gene of interest but bind other TFs to enhance transcription

Front 162

Mediators

Back 162

modify histones to allow for transcription

Front 163

Chromatin remodelers

Back 163

move nucleosomes to allow for transcription

Front 164

Peptide bond

Back 164

Links the Carboxylic acid of one AA to the amino end of the next AA

releases water

bond is Carbon-Nitrogen

Front 165

tRNA Structure

Back 165

Hairpin loops

carry the amino acid encoded for by the codon on it's 3' end

anticodon on tRNA inteacts with codon on mRNA

Front 166

Ribosomes

Back 166

most important part is the RNA component

the rRNA catalyzes formation of peptide bonds

Front 167

Initation of translation

Back 167

initator tRNA and small subunit bind mRNA and move along mRNA until START codon is found

once found, large subunit binds (initator tRNA n P site)

next tRNA moves to A site

Front 168

Translation steps

Back 168

after intiation, bond forms

large subunit moves down mRNA (1st AA to E site, 2nd AA to P site)

Small subunit moves down mRNA

3rd AA to A site

Bond forms

repeat until stop codon

Front 169

Post transcriptional modifcations

Back 169

5' Cap and Poly A tail

prevent degradation of mRNA so it can actually be translated

Introns removed in nucleus

Front 170

Splicing

Back 170

Done by splicecome (many snRNPs together)

removal of introns

Typical sequence for ends of an intron is: GU (acceptor) and an AG (donor)

Front 171

5' cap placement

Back 171

aka 7-methylguanosine cap

goes at the beginning of the exon REGARDLESS OF IF THE FIRST 3 BASES CODE A START CODON

Front 172

Changes that transmit info in signalling

Back 172

1) post translational modifications

2) protein binidng

3) concentration and location of protein in cell

4) conformation of protein

5) enzymatic activity of protein

6) 2nd messengers

Front 173

Linked Changes

Back 173

one modifcation combines with another modifcation to change activity

(ex. phosphorylation causing a conformational change)

Front 174

Post-translation modifications in signaling

Back 174

Phosphorylation

acetylation

methylation

ubiquitination

proteolytic cleavage

Front 175

why phosphate?

Back 175

big, negatively charged (-2) molecule (binding will have big effect)

ATP readily available as donor

easily controlled by enzymes

occurs primarily at -OH on Ser, Thr, and Tyr

Front 176

Tyrosine Phosphorylation

Back 176

less than 1% of phosphorylation

only found in multicellular organisms

involved in adhesion, proliferation, and hormone response

Front 177

Ubiquitiniation

Back 177

used to mark proteins for degradation

many can be linked together

linked at c terminus to lysine residues

Front 178

Kd

Back 178

dissociation constant

[Product]/[substrates]

high Kd, low affinity

when cocentration is > Kd, mostly product

when concentration < Kd , mostly substrates

big range

Front 179

Affinity

Back 179

Measure of how likely 2 components are to bind together

absolute property of an enzyme

Front 180

Specificity

Back 180

measures affinity of an enzyme for one substrate vs another substrate

its relative!

Front 181

Subcellular localization of proteins

Back 181

activity will increase if a protein is concentrated somewhere

Front 182

STATS

Back 182

ligand binds receptor

activates JAK tyrosine kinase

PO4 of STAT

dimerization of STAT and translocation to nucleus

STAT serves as a transcription factor

Front 183

Calmodulin

Back 183

calcium sensor

changes conformation when binding calcium

Front 184

Second messengers

Back 184

Small, rapidly diffusible molecules that cause SIGNAL AMPLIFICATION

exs: cAMP, Calcium, DAG, IP3

Front 185

GPCR

Back 185

7 TM protein, associated with heterotrimeric G protein IC. binds ligand, G protein swaps GDP for GTP, dissociation of subunits, causing effects in the cell (transcription, phosphorylations, etc)

Front 186

PLC (phospholipase C)

Back 186

activated by g protein

cleaves PIP2 to IP3 and DAG

DAG is a dock for PKC

IP3 causes calcium release from ER

Front 187

SH2 domain

Back 187

Binds phosphotyrosines

Front 188

SH3 domains

Back 188

bind proline rich peptides

Front 189

Adaptor Proteins

Back 189

couple phosphotyrosines to effector proteins via SH2 and SH3 domains

Front 190

Scaffold protiens

Back 190

force enzyme and substrate to be near each other, increasing specificty

Front 191

G proteins

Back 191

have inherent GTPase activity

Front 192

GAP

Back 192

puts GDP on G protein

inactivates the g protein

Front 193

GEF

Back 193

puts GTP on G protein

activates the G protein

Front 194

Small G protein

Back 194

Monomeric

activated by GTP, inactivated by GDP

involved in signalling (Ras, Rac, Rho)

Front 195

Classic Beta Adrenergic receptor

Back 195

epinephrine binds receptor

alpha subunit of G protein swaps GDP for GTP

alpha dissociates from beta/gamma and activateds adenylate cyclase

AC converts ATP to cAMP

cAMP activates PKA

PKA can phosphorylate other proteins like CREB

CREB binds DNA to affect transcription

Front 196

Diffusion across the membrane

Back 196

very small, nonpolar molecules like Nitric Oxide can cross

Steroid hormones can as well

Front 197

Steroid hormones

Back 197

Bind cytoplasmic receptors

translocate into nucleus to affect transcription

Front 198

Dimerization of receptors

Back 198

Some receptors have inherent kinase activity

they dimerize when the ligand binds and autophosphorylate tyrosines on the receptor

SH2 domains on proteins can dock on the receptor

Front 199

Ras activation cascade

Back 199

RTK activated by signal molecule

grb is adapter protein (SH2 domain links to receptor, sh3 domain links to SOS)

SOS is a GEF for RAS and activates it

Front 200

Ras functions

Back 200

regulates proliferation and differentiation

Front 201

PKB/Akt

Back 201

RTK activated by ligand binding. allows PI3k to bind receptor. PI3K phosphorylates PIP2 to PIP3

PDK1 and and PKB dock on PIP3, PDK1 phosphorylates PKB and activates

PKB un-docks and Phosphorylates BAD, which releases proteins that inhibit apopotosis

Front 202

Fractional occupancy

Back 202

= [B]/(Kd+[B])

Front 203

PH domains

Back 203

bind specific phosphinositol lipids

Front 204

PROTEOGLYCAN AGGREGATES

Back 204

Hyaluronan and proteoglycans (attached by linker protiens)

abundant in the ground substance of cartilage, allowing for resistance of compression and flexibility (excellent shock absorbers)