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63 Cards in this Set
- Front
- Back
work performed by molecular motors
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muscle contraction (myosin and actin)
eukaryotic cell migration, sperm motility, and fluid flow (dynein motors and tubulin ropes) intercellular vesicle trafficking (myosin motors and actin ropes or kinesin and dynein motors with tubulin ropes) |
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Hierarchy of mucle structure
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Muscle cells = myofiber = multinenculeated, 150-100 micrometers wide and up to several cm in length
--cells are bundles of myofribrils; myofribrils are composed of linearly linked sarcomeres |
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sarcomeres
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Z line
I band (just thin filament, disappears) A band (thick filament, always same length) H zone: area of just thick filament, shrinks |
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actinin
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anhcors thin filaments to z disc
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titin
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connects z disc to thick filaments; positions myosin relative to thin filaments
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nebulin
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"molecular ruler"; regulates length of thin filaments
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Dystrophin
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anchors array of myofibrils to plasma membrane
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Myosin
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6 polypeptides: two heavy chains, two regulatory light chains, 2 essential light chains
-regulatory light chains only regulatory in smooth muscle --heavy chains form coiled coil of helices |
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Stable fragments of myosin
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treat with papain and trypsin
Two S1 subframents: N-terminal portion of a heavy chain, one essential light chain and one regulatory light chain; it is the motor S2 fragment and light meromyosin fragments: contain portions of the two heavy chains that form the coiled coil tail |
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Larger overall myosin structure
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bundle together to form the thick filament of striated muscle; coiled coil regions form back bones and S1 motors (300 per filament) extend radically from backbone
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Structure of S1 fragment
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P-loop contains NTPase domain
Alpha helix had binding site for the two light chains |
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Myosin light chain structure
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similar to that of calmodulin. All three (regulatory, essential, calmodulin) bind an alpha helix by wrapping around it.
essential light chain binds 1 calcium; regulatory light chain binds 1 magnesium; calmodulin binds 4 calcium |
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Protein composition of thin filament
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G-Actin assembles into a chain of F-actin, which dimerizes to form a helical structure; tropomyosin and troponin are then bound to form the thin filament
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crossbridge cycle
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Relaxed muscle: weak myosin crossbridge, ADP and Pi bound-->calcium triggers Pi release-->myosin binds to actin (strong myosin crossbridge)-->ADP is release, resulting in power stroke-->rigor state with strong myosin crossbridge and no atp bound-->atp binds, myosin detaches from actin, weak myosin crossbridge-->atp hydrolysis leads to cocking of the lever arm
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structural basis for myosin movement
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rotation around a relay helix to create the movement is made possible with the release of phosphate from the complex, causing allosteric changes
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ATP
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only thing that can be used by myosin
-creatin kinase can replenish stores --in anaerobic conditions adenylate kinase converts two adp into an amp and an atp |
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Myosin I motors
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single head moleucles lacking the coiled coil carboxyl tail. Its terminal end is a lipid binding domain associated with vesicles
--attaches vesciles to actin tracks criss-crossing cells. attach and detach from actin in much the same way as myosin II, dragging vesicles along tracks --regulated by Ser/Thr phosphorylation |
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Regulation of muscle contraction in smooth muscle
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thick filament based via calcium dependent phosphorylation of the myosin regulatory light chain
calcium-->calmodulin binds myosin light chain kinase-->phospohrylates light chain myosin, inducing cross bridge cycling |
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Regulation of contraction in striated muscle
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thin filament based via calcium binding to the troponin complex
calcium binds troponin C-->acts on tropomyosin to make actin available to myosin heads --calcium induces conformational change in troponin c, which pulls troponin T (attached to tropomyosin) into a different conformation, thus revealing myosin binding sites. Troponin I binds troponin to the actin filament |
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General Collagen Facts
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25 different collagens
--type I-IV make up 90% of human collagens --types I, II, and III are fibril forming --type IV is network forming --**all collagens contain 3 polypeptide chains ***all collagens have at least one triple helix domain |
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Type I collagen
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fibril forming
major component of skin and bone |
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Type II collagen
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Fibril forming
Primarily in Cartilage |
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Type III Collagen
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Fibril forming
Found in blood vessels Key role in wound healing |
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Type IV
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Network forming
--basement membranes of cells--"the basal lamina" |
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Collagen I-III common characteristics
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~1000 amino acids in each chain
--each individual cahin is an alpha-chain --3 alpha chains = mature collagen --every third amino acid is Glycine --20% proline/hydroxyproline --1-5% hydroxylysine |
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Collagen helix
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Gly-X-Y is repeating pattern
--very different from alpha helix 1. more extended 2. no intrachain hydrogen bonds 3. stabilized by steric repulsion of pyrrolidone rings 4. collagen helix is essentially tertiary structure |
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Collagen triple helix
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3 alpha chains come together
--rod shaped, 3000 angstroms long, only 15 angstoms wide --glycine found at interface between the three chains (only one small enough --hydrogen bonded together by the NH of glycine to the C=O of other residues --hydroxyproline also has hydrogen bonds |
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Hydroxylation of proline and lysine
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requires Ascorbic acid (vitamin c acts as a co-enzyme)
prolyl hydroxylase and lysyl hydroxylase hydroxylate the two AA |
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hydroxylated lysine
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provides the site for O-glycosylation of the collagen strand
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Formation of collagen
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--Translated
--once completely translated, hydroxylated, glycosylated, then triple helix formation is initiated at the globular, C-terminal domain --procollagen is assembled within the cell. triple helix in center with n-terminal and c-terminal globular domains (these are stabilized by disulfide bonds) --procollagen secreted, propeptides at either end are cleaved by procollagen peptidases --this forms tropocollagen. tropocollagen is packed into collagen fibrils which are then organized into mature collagen |
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Collagen fibril cross-linking
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-crosslinking stabilizes structureal rigidity
--key step is enzymatic formation of aldehyde derivatives of lysine and hydroxylysine. --subsequent crosslinking is non-enzymatic --(lysine-->allysine (reactive aldehyde) by lysyl oxidase-->aldol cross liniks lysinonorleucine, or more complex structures |
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Collagen type iv
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networking collagen
--protomer has globular domains at c terminus with n-terminal triple helix; dimerizes to form carboxy terminal hexamer; networks to form collagen tetramer, which network to form suprastructure --has 7S domain and NC1 hexamers |
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Elastin
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-found in elastic fibers in ECM ofh ihgly elastic tissue such as smooth muscle and lung
-tropoelastin precursor --alternating hydrophilic and hydrophobic domains --tropoelastin secreted, aligns with microfibrils and then is crosslinked in reactions analogous to those for collagen --forms amophous fibrous mesh encircling cells --elasticity due to functional structural instability of alternating domains (hydrophilic domains give it the springy character) |
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Laminin
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---heterotrimeric with alpha, beta, and gamma subunits
--binds to and crosslinks other proteins in the basal laminae --helical regions in each subunit form triple helix domain; coiled coil is stabilized by disulfide bonds --all three subunits have n-terminal globular extension; alpha subunit also has c terminal globular domain --globular domains interact with other extracellular and cell surface proteins to connect the basal laminae to the cell |
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Proteoglycans
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--polypeptide chain with large number of covalently bound polysaccharides (95% polysaccharide by weight)
--polysaccharides may be sulfated and carboxylated to provide negative charages --major component of ECM of tissues such as arterial wall, bone, cartilage, and ysnovial fluid of joints --form a gel in which other ECM proteins are embedded. gel provides mechanical support, allows diffusion of small molecules, but restricts diffusion of larger proteins |
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Glucosaminoglycans and Proteoglycan structure
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--the long polysaccharides attached to proteoglycans
--repeating disaccharide units, frequently sulfated --usually attached to a serine or threonine residue in the core protein via a trisaccharide linker. exception is hyaluronic acid, which isn ot linked to a protein --glycosylation occurs in the ER --sulfation occurs after addition of the sugar units --mature proteoglycans have bottle brush appearance --proteoglycans sometimes attached to hyaluronic backbone via "linker proteins" |
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Integrins and adhesion proteins
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--membrane proteins that link cells to ECM
--attach to adhesion proteins such as fibronectin --alpha beta heterodimer. there are 18 different alpha subunits and 8 beta subunits --two way sensor activity in which intra and extra cellular events recognized --due to their role in cell adhesion and cell migration, important in cancer |
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osteogenesis imperfecta
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Disease caused by mutations in the collagen gene
--has multiple types. types I, III, and IV may live well into adulthood. Type II is fatal at birth (all bones broken at birth). --changes of glycine residues, especially near c-terminal end, often results in fatal form --brittle bones, blue sclera, dental abnormalities, progressive hearing loss, eye disorders |
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Ehler Danlos
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Collagen problem
--hyperflexibility of joints --hyperplasticiity of skin --blue slcera |
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Extracellular matrix
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--determiens shape and elasticity of tissues
--bone=mostly ECM --matrix of CT includes basal laminae --contains proteins that provide structural support, elasticity, adhesion, and anchorage/communication |
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Nucleoside bond
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Beta glycosidic linkage
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Zydovudine
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aka Asizdothymidine aka AZT
HIV treatment |
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Dideoxyinosine
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HIV treatment
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Acyclovir
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antiviral for things like herpes
mimics guanosine |
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5-Fluoroacyl
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mimics uracil
cancer treatment |
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ultraviolet absorbance by DNA
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highest at 260 nm
Single strand greater than double strand Tm (50% melted) at ~71 degrees centigrade |
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Effect of alkali on DNA and RNA
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DNA strands stay intact, but separate
RNA strands are degraded to nucelotides due to presence of 2' hydroxyl group. |
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nucleosome core particle
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140 bp around nucleosome core (octamer of histones)
60 bp spacer between nucleosome (beads on a string) H1 associates with spacer |
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polynucleosome
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higher order of chromatin structure
nucleosomes further coil into solenoids |
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Human genome
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3 billion bp per haploid genome, ~25000 genes
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centromere
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where sister chromatids connect
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DNA replication
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--semiconservative
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helicase
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unwinds DNA, ATP dependent, results in supercoiling
bacterial helicase PerA: domains A1 and B1 bind single stranded DNA; bind atp come together, hydrolyze atp come apart, pulling dna apart |
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Single strand DNA binding proteins
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keep strand from re-annealing
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Topoisomerase I mechanism
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--relieves torsional stress by cutting and re-ligating single strand of DNA
--does not require ATP --inhibited by campothecin (anticancer drug) |
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Topoisomerase II mechanism
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--binds DNA at gate segment (G segment). Binds ATP, cleaves both strands of g segment and binds T segment, which it loops through break in G segment before hydroylyzing ATP and closing the gap it made
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Etoposide
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cancer drug that inhibits mammalian topoisomerase II by preventing religation. widely used in treatment of lung, ovarian, testicular, prostate cancer
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DNA gyrase
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topoisomerase found only in prokaryotes
--Quinolone antibiotics (e.g. ciprofloxacin) inhibit DNA gyrase, used for infections |
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DNA Ligase
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--attached 3' hydroxyl to 5' phosphate using ATP to AMP in eukaryotes and archaea and NAD to AMP and NMN in prokaryotes
--hydrolyzes AMP and binds it to lysine on enzyme; transfers it to phosphate, replaces it with phosphodiester linkage |
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Bacterial DNA Pol I
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filling of gap after removal of RNA primer, DNA repair, removal of RNA primer in conjunction with RNase H
exonuclease activity in both directions |
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Bacterial DNA Pol II
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--DNA repair
exonucleause in 3 to 5' direction |
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Bacterial DNA Pol II
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replication--synthesis of DNA
3 to 5 exonuclease activity |
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Taxol
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chemotherarpy agent prevents cytoskeletal remodeling during mitosis
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