MBB 222 lec 10 protein secondary structure

where are the points of flexibility in peptide backbones? Where is rotation not possible?

-lack of rotation around peptide bond (due to partial double bond character, pi bonds cant rotate)

-points of flexibility: along backbone of protein IN BONDS to a-carbon

-2 specific bonds: N-Ca (phi) and C-Ca (psi)

(remember psi=C because s and c make same sound)

-allows proteins to fold many ways

when can rotation occur and not occur in peptide bonds?

-when unfolded can rotate/fold via phi and psi bonds (N-Ca and C-Ca)

-when folded, ROTATION USUALLY RESTRICTED

two characteristics (physical) of peptide bond? (hint. due to the reason it cant rotate freely)

-RIGID and FLAT (due to partial double bond character)

-remember: rigid cause cant rotate, and flat because no rotate in other shapes

torsion angle

aka dihedral angle

-describes how 2 parts of a molec TWIST RELATIVE TO EACHOTHER

what changes path of polypeptide chain?

-rotation around the phi and psi torsion angles

what configurations are possible for peptide bond?

trans and cis

which configuration is more common in peptide bonds? describe the two configurations

trans is more common (minimize steric clashes between adjacent R groups)

cis is RARE (place R groups on SAME SIDE of peptide bond, causing steric strain) exception: proline

-steric means relating to arrangement of atoms

Ramachandran plot

-plots all possible combinations of phi and psi angles

-reveals what conformations are sterically permitted

25% or 50% or 75% or 90% of phi/psi combinations are forbidden? why?

75% due to steric clashes (mainly between backbone atoms and side chains)

what does the open space in ramachandran plots mean?

space=not allowed

what do the allowed regions in ramachandran plot correspond to

common secondary structures (like B sheets and right handed a-helices)

what amino acid occupies a larger allowed space (as shown in ramachandran plot)

glycine (due to minimal side chain)

the secondary structure desribes the _____ of the polypeptide backbone

describes the LOCAL ARRANGEMENT (how it folds) of polypeptide backbone into repeating conformations

3 most abundant secondary structures in proteins

B strands, a helices, B turns

-literally looks how they sound, strand is just a line, helix twists like helix, B turn is just a turn (looks like letter C)

the a-helix is a

repeating COILED structure stabilized by HYDROGEN BONDS (intra-chain)

the a helix is stabilized by

intra-chain H-bonds between main chain O in carbonyl (C=O) and the amide H of NH group

do peptide bonds have dipole moments?

yes each peptide bond has a dipole moment (O is partially -, N is partially +)

-in a-helix, these dipoles are aligned in SAME DIRECTION

what creates overall helix dipoles?

-alignment of many peptide dipoles (from O and N)

-N terminus=partially positive (b/c its the base so accepts proton)

-C terminus=partially negative

what is “handedness” in a-helices?

-just like dipoles point in 1 direction, the backbone twits IN ONE CONSISTENT DIRECTION

-that twist gives helix “handedness”

are protein a-helices right or left handed spirals? why

right-handed spirals (as u move from N to C terminus, helix twists CLOCKWISE) (clockwise=go to right, remember that)

The helix contains how many residues per turn and rises how many A per turn?

3.6 residues per turn

rises 5.4 A per turn

why does backbone geometry of protein naturally favor a right-handed helix?

b/c all amino acids in proteins are L-amino acids

Phi angle is the rotation around ______ and defined by these 4 backbone atoms:

rotation around N-Ca bond

defined by:
C’ (i-1) - N (i) - Ca (i) - C’ (i)

Psi angle is rotation around _______ and defined by these 4 backbone atoms:

rotation around Ca-C’ bond

defined by

N (i) - Ca (i) - C’ (i) - N (i+1)

what is the reason hydrogen bonds form every 4 residues?

3.6 residues per turn

phi and psi angles determine

overall direction of polypeptide chain

what gives rise to alpha helices, beta sheets, and other secondary structures

different combinations of phi and psi angles (dihedral torsion angles)

on a ramachandran plot for a helices, each dot represents

the phi and psi backbone angles of ONE amino acid residue

if a protein has 80 residues, how many dots will u see on the ramachandran plot

80

where do most a-helices cluster in a ramachandran plot? and what are aprox angles of phi and psi angles?

right handed helical region

-phi approx -60 and psi approx -45

-these angles position backbone correctly to allow stable i to i+4 H bonding, stabilizing a-helix

which 2 amino acids are less common to see in a-helices?

glycine and proline

why are glycine and proline less frequently found in a-helices than other amino acids?

glycine - no side chain (only H) so TOO FLEXIBLE (harder to maintain helical shape)

proline - backbone N is part of ring and LACKS AN H, so cant donate H bond into helical backbone (breaks H-bonding and introduces a kink, hence “helix breaker”)

although a-helices are stabilized mainly by ______, ________ modulate/influence how stable a helix is

stabilized mainly by H-bonds

side chains modulate how stable

helical wheel projection

2D diagram representing an a-helix viewed down its long axis, showing relative positions of aa side chains around the helix (helical wheel represents R groups)

Amphipathic helices

a-helices with hydrophillic aa on one side/face and hydrophobic aa on the other

what kind of a-helices are often the membrane-binding domains of membrane proteins?

amphipathic a-helices (hydrophillic head and hydrophobic carbon chain)

motif

small recurring combo of secondary structure elements that appear in many diff proteins

a-keratin is

a stable structure formed by a-helices entwined

-found in hair, nails, etc

(2 helices wind around another to form SUPER HELIX)

how many amino acid residues repeated in a-helical coils

7 (heptameric)

B strand consists of

an EXTENDED polypeptide chain

are B strands twisted or planar? why?

TWISTED (not completely planar)

-they twist b/c ideal PHI/PSI angles and STERIC CONSTRAINTS make flat sheet energetically unfavourable

why would a flat B-strand sheet be energetically unfavorable?

b/c of phi psi angles and steric constraints

are adjacent amino acids on same or alternate sides of B strand?

alternate

B strand is the basic unit of

B sheet

how are b-sheets stabilized? (easy)

-H-bonds between main chain amide atoms (like a-helices)

what is B sheets peptide backbone made of

peptide backbone made of B strands

are strands parallel or antiparallel in B sheets

can be either (have a combination of both)

-parallel looks like all arrows (C terminus) pointing same way)

just like a-helices, the side chains in B sheets are NOT part of the ________ that hold B-strands together

H bond network

how does H bonding differ in a helices to B sheets? which requires more extended backbone conformations?

a-helices: INTRA H-bonding

B-sheets: INTER H-bonding between diff strands (more extended backbone conformations so phi/psi angles occupy diff region of ramachandran plot)

Why do beta sheets have larger area of possible phi/psi angles than alpha helices?

b/c their backbones are more EXTENDED and FLEXIBLE

-a helices require very SPECIFIC dihedral angles to maintain their tightly coiled H-bonding pattern

why do a-helices have smaller area of possible phi/psi angles

b/c they require VERY SPECIFIC phi/psi angles to maintain their TIGHTLY COILED H-bond pattern

is this anti or parallel B sheet: H bond connect an aa on one strand to TWO DIFF aa on the adjacent strand

parallel

which B sheet arrangement (parallel or anti) has stronger H bonding pattern?

Anti parallel

-b/c they are more linear (better geometry)

-form direct 1 to 1 H bonds

SO they are more stable/stronger than parallel sheets that are bent

Because ______ stick out on either face of B sheets, they can give diff ______ to each face

R groups stick out so they can give diff properties (polarities) to each face (ex. one side hydrophobic one side hydrophillic)

strands of B sheets tend to be twisted and inclined, esp in a:

B-barrel

explain Porin, the bacterial transmembrane protein

forms selective channel in outer membrane

-hydrophobic side chains line OUTER surface to interact w lipid bilayer

-hydrophillic side line INNER channel

(think water on inside)

explain B-sandwich

-2 B sheets stacked upon eachother

-side chains pointing “inside sandwich” must be complementary (they can interact w eachother, often hydrophobic to avoid aq surroundings)

fibroin amino acid sequence has repeats of:

Gly-Ala-Gly-Ala etc

-random fact: fibroin fibers are spun by spiders

how do B sheets stack in fibroin

glycine side chains and Ala side chains from opposing faces INTERDIGITATE (fit tgt like interlocking fingers)

explain interdigitate

fitting tgt like interlocking fingers (think digital=fingers type on digital computer)

-ALLOWS FOR CLOSE PACKING OF SHEETS

alpha keratin vs beta keratin

alpha keratin: hair/nail/horn of MAMMALS (think mammals are alpha big animals)

-primarily a helices

beta keratin: feathers/claws/beaks/scales of BIRDS/REPTILES (think beta for bird)

-combos of parallel/anti-parallel beta sheets (think combo of strands, combo of animals (birds and reptiles)

one similarity and one difference between a-keratin and b-keratin

-do similar jobs: structural support, barrier function

-aa sequences vry diff b/c evolved to form diff secondary structures

B turn

a SHORT segment of FOUR aa’s

-allow polypeptide chain to REVERSE DIRECTION

B-turn is the reason proteins can: (3 things)

-CHANGE direction

-CONNECT B strands and a helices

-stay COMPACT instead of stretching out

(think B-turn does CCC, change, connect, compact)

How can u tell apart type I vs type II B-turns?

differ in backbone dihedral angles and carbonyl orientation:

-type I has carbonyl O pointing INWARD

-type II has carbonyl O pointing OUTWARD (and often requires GLYCINE at position i+2 to AVOID steric CLASH)

What do type I and II B turns have in common

-both stabilized by an H bond between residue i and i+3 (allowing chain to REVERSE DIRECITON)

Loops vs B turns compare

LOOPS ARE LARGER and not as tight (more than 4 aa in loops)

-same function of connecting a helices and B strands

where are Loops usually located on proteins?

SURFACE where aa side chains can interact w/ solvent molecules of other proteins

LOOPS form connections between:

diff secondary structures like parallel and antiparallel B sheets

LONGER LOOPS may contain

ordered a-helices (sometimes with beta turns)

do loops often have regular repeating turns or irregular nonrepeating turns

IRREGULAR, not repeating

true or false: LOOPS often connect a helices with B strands, a helices with a helices, and B strands with B strands

true