Three Dimensional Structure Of Proteins

Front 1

physiological roles of proteins

Back 1

1. enzymes
2. storage & transport
3. physical cell support & shape
4. mechanical movement
5. decoding cell information
6. hormones and or hormone receptors
7. other specialized functions

Front 2

protein size

Back 2

typically 100-1000 amino acids in length. (smallest protein is insulin with 51 mamino acids, largest is titin with 34,350)
dividing molecular weight of protein by 110 is approx the number of amino acids

Front 3

five important facts about proteins

Back 3

-the three dimensional structure of a protein is determined by its amino acid sequence
-the function of a protein depends on its structure
-an isolated protein usually exists in one or a small number, of stable structural forms
-the most important forces stabilizing the specific structures of a given protein are non covalent
-within the huge number of protein structures there are common structural patterns

Front 4

stability of a protein

Back 4

not the sum of the energies of formation of the many weak interactions but rather the difference in the free energies of the folded & unfolded states.
the protein conformation with the lowest free energy (the most stable) is usually the one with the max number of weak interactions
weak interactions predominate as a stabilizing force in protein structure

Front 5

proteins folded by a rapid stepwise process

Back 5

folded proteins occupy a low energy state that makes the native structure most stable
this state is only marginally stable. some proteins can spontaneously fold to the native conformation, others require the help of chaperone proteins (help proteins maintain correct conformation, assist in unfolding). protein folding is a rapid process.
individual secondary structures form first then hydrophobic core condenses to give tertiary structure. protein folding and unfolding is a cooperative process

Front 6

protein denaturation & folding

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denaturation- disruption of native conformation with loss of activity
energy required is small, perhaps only equivalent to a few hydrogen bonds.
denaturaring is a cooperative process
some proteins can be renatured

Front 7

four levels of protein structure

Back 7

primary- linear sequence of amino acids
secondary- localized interactions within the polypeptide chain
tertiary structure-final structure (folding pattern) of a single polypeptide. for most proteins, highest level of structure they will achieve
quaternary structure- folding pattern with mulitple polypeptides (more complex functions/structures)

Front 8

primary structure

Back 8

defines the linear arrangement of amino acids but tells nothing of the three-dimensional structure
within the main chain there is a repeating structural pattern of NCCNCC
presented from N-C terminus

Front 9

secondary structure

Back 9

regularities in local conformation maintained by main chain hydrogen bonds between amide hydrogen & carbonyl oxygen groups
regions of secondary structure are characterized by a specific pattern of hydrogen bonding
folding of a polypeptide is restricted by the limited flexibility of the peptide bond
the major examples are the alpha helicies and beta sheets

Front 10

two rules for formation of secondary structure

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1) optimize the hydrogen bonding potential of the main chain carbonyl & amide groups (side chains arent worried about; look at main chain) can form a hydrogen bond, MUST form a hydrogen bond
2) represent a favored conformation of the polypeptide chain

Front 11

conformation vs configuration

Back 11

conformation: spatial arrangement of groups that are free to assume different positions in space without breaking bonds. the possible conformations of a protein include any structural state that can be occupied without breaking covalent bonds
native conformation: each protein folds in a single stable shape (physiological conditions)
configuration: spatial arrnagement of atoms around double bonds or chiarl centers, can only be changed by breaking bonds

Front 12

configuration of the peptide bond

Back 12

rotation around C-N bond is restricted due to the partial double bond nature of the peptide bond (no freedom of rotation). the 6 atoms of the peptide group are planar, the oxygen of the carbonyl group & the hydrogen of the amide nitrogen are trans to each other
the side chain groups also end to be in the trans configuration

Front 13

configuration of the polypeptide chain

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each alpha carbon is held within the main chain through single bonds, about which there is complete freedom of rotation.
these bonds are defined as Phi and Psi

Front 14

the peptide bond and hydrogen bonding

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each peptide bond has both a hydrogen donor as well as a hydrogen bond acceptor. there are an equal number of hydrogen bond donors and acceptors within the polypeptide main chain which is important from the perspective of optimizing hydrogen bonds

Front 15

alpha helix

Back 15

right handed helix, 3.6 residues per turn
first type of secondary structure proposed or governed. each C=O forms a hydrogen bond with the amide hydrogen
helix is stabilized by many hydrogen bonds which are nearly parallel to long axis of the helix

Front 16

amino acid sequence and helix stability
rules and trends

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-proline, because of its rigidity, is known as a helix breaker it is not usually found in alpha helicies
-glycine, because of the flexibility it imparts, is usually not found in alpha helicies
-stretches of similarly charged residues are not observed as they will destabilize the helix due to the electrostatic repulsion
-residues separated by 3-4 positions in the primary structure are close together in helical structure: positively and negatively charged residues found in 3 or 4 positions away from each other
-aromatic residues also often separated by 3 or 4 positions to enable hydrophobic interactions

Front 17

the helix dipole

Back 17

a small electrical dipole exists in each peptide bond. this dipole is communicated through the helix by hydrogen bonding. as a result, the helix has a net dipole where by the N terminus of the helix carries partial positive charge, the C terminus carries partial negative charge. the sequence of the helix can help stabilize this dipole by the positioning of charged residues at these termini

Front 18

constraints on the alpha helix stability (summary)

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1. electrostatic repulsion (or attraction) between successive residues with charged R groups
2. the bulkness of adjacent R groups
3. the interactions between residues spaced by 3 or 4 residues
4. the occurrence of proline and glycine
5. the interaction between amino acids at each end of the helix and the helix dipole

Front 19

conformation of B strands

Back 19

polypeptide chains that are almost fully extended. B sheet side chains project alternately above & below the plane of the B strands. one surface of a B sheet may consist of hydrophobic side chains (amphipathic B sheet)

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Parallel and Anti Parallel B strands

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B strands in a sheet are parallel or anti parallel

parallel- strands run in same N to C direction
anti parallel- strands run in opposite N to C direction. they are more stable due to better geometry of hydrogen bonding

Front 21

tertiary structure

Back 21

the final folding pattern of a single polypeptide chain
describes the longer range aspects of sequence interactions within a polypeptide chain
residues separated by great distance in primary structure may be in close proximity in tertiary structure
amino acid sequence determines tertiary strucutre

Front 22

Quaternary structure

Back 22

composed of multiple subunits where each subunit is a separate polypeptide chain
may have multiple sub units of the same type of polypeptide or be composed of diff types.
subunits held together by non-covalent interactions. typically reserved for more complex proteins : specific & discrete interactions between the different polypeptide chains

Front 23

advantages of Quaternary strucuture

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1) may help stabilize subunits & prolong life of protein
2) unique active sites produced at interface between subunits
3) help facilitate unique & dynamic combinations of structure/function through physiological changes in tertiary & quaternary structure (hemoglobin)
4) conservation of functional subunits more efficient than selection for new protein with ideal function

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keratin

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fibrous protein (holding things together)
principle component of hair, wool, horns and nails.
linked together by disulfides. the extent of these bonds will determine the strength of the overall structure

Front 25

keratin primary structure

Back 25

primary strucutre: keratin contains a pseudo-seven repeat where positions "a" (1) and "d" (4) are hydrophobic (non polar)

Front 26

keratin secondary structure

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forms right handed, amphipathic alpha-helicies. residues from positions "a" & "d" end up on the same face of the helix resulting in a hydrophobic strip along the length of the helix

Front 27

keratin tertiary strucuture

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dominated by the polypeptide strand presenting on alpha helicial rod. the hydrophobic strip running the length of this rod is looking for a hydrophobic environment

Front 28

quaternary strucuture

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pseudo seven repeat gene rates hydrophobic surfaces along the length of the helix. through these hydrophobic surfaces interact to the formation of a coiled coil; it involves two right handed helicies wrapping around each other in a left handed fashion

Front 29

collagen

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fiborous protein
major protein of vertebrates (25% of total protein) diverse forms include tendors (rope life fibers) and skin (loosely woven fibers)
these linkages occur from amino acid residues that undergo post translational modification instead of disulfide bonds
more of these cross links occur with age, hence the affects of aging

Front 30

primary structure of collagen

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multiple repeats of Gly-X-Y where X is often proline and Y is often hydroxyl proline

Front 31

secondary structure of collagen

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formation of left handed helicies of three residues per turn (as opposed to the 3.6 right handed alpha helicies)

Front 32

tertiary structure of collagen

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nearly the full length of the polypeptide is helicial

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quaternary structure of collagen

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formation of coiled-coils. three left handed helicies wrapping around each other in right handed fashion

Front 34

post translational modifications of collagen

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the enzyme that performs post-translation requires vit C, Vit C deficency leads to defective triple helix (skin lesions, fragile blood vessels, bleeding gums)

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scurvy

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symptoms include: numerous bruises, tooth loss, poor wound healing, bone pain & eventual heart failure
milder cases cause fatigue, irritability, & susceptibility to respiratory infections.

Front 36

genetic diseases involving collagen

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osteogenesis imperfecta, marfan's syndrom, stickler syndrom & ehlers-danlos syndrome.

associated with brittle and abnormal bone structure, weakened cardiovascular capabilities, abnormal facial features, loose skin & joints, hyperflexibilty

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silk

Back 37

silk fibroin is produced by insects and spiders for formation of webs & cocoons. these structures require both strength and flexibilty

Front 38

silk primary strucuture

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most silk has a 6 residue repeat that is rich in small amino acids

Front 39

silk secondary strucutre

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silk is composed primarily from beta-sheets. the fully extended polypeptides of the beta strands offer considerable strength. silk has a very high strength yet it is still highly flexible

Front 40

structure of silk

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1) fully extended polypeptide chains (strength)
2) association of strands by hydrogen bonding (flexible)
3) association of sheets by van der waals forces & hydrophobic interactions (flexible)

Front 41

Prion diseases

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transmissible spongiform encephalopathers (TSEs)
- represent a novel paradigm of infectious disease based on misfolding of a self-protein into a pathological infectious conformation