1) Introduction

what type of bond is the strongest in list of interactions?

covalent bond

protein structure vs 3d structure

protein = amino acid sequence

folded protein = 3d structure = function

T/F: when you crystallize something, it maintains structure and function

True

learned by James Summer crystallizing protein, its activity was unchanged

primary, secondary, tertiary, quaternary protein structure

primary: amino acids in sequence

secondary: alpha and beta sheets

tertiary: multi-chain domains that come together for final protein

quaternary: arrangement of 2 or more separate folded polypeptide chains into larger functional complex

details on peptide bonds (how are peptide bonds formed)

ribosomes form peptide bonds

backbone carbon group attached to N terminus forms planar arrangement, double bond is shared and becomes delocalized

what is a ramachandran plot? how do you read it?

XY plot, used to evaluate the structural quality of proteins, mapping backbone dihedral angles, phi on the x axis and psi on the y axis

darker regions represent areas where the angles are favourable (no crowding or collisions)

each dot represents a single amino acid in the protein
- alpha helices = clusters in lower left quadrant (negative phi and psiW)
- beta sheets = clusters in the upper left quadrant (negative phi and positive psiW)
- left handed alpha helices = small islands in upper-right quadrant (positive phi and psiW)

what are some special amino acids in rachmandran plot

glycine has tiny hydrogen atom on side chain, very flexible and dots can spread far outside the standard favoured regions into otherwise disallowed spaces

proline side chain forms rigid ring with the backbone nitrogen, limiting rotation and restricting to tighter clusters

explain this example

left is general of all amino acids minus proline and glycine

right is just glycine, with more blobs around due to higher flexibility of glycine

what are alpha helices? what are details on them?

chain of amino acids twisted into spiral

most are right handed
distance between amino acids = 1.5A
carbonyl groups point down, R groups outside

functions as spring or hinge point (flexible)

difficult to predict structure of alpha helices

Pro and Gly often destabilize alpha helices, can expand structure or break it entirely

what are beta sheets? what are details on them?

two or more polypeptide chains lie side by side, bound by hydrogen bonds

can twist/bend or be flat

distance between adjacent amino acids is 3.5A

can be parallel or antiparallel

what are loops and turns? what are details on them?

short directional loops and connecting other structures

can be rigid or flexible

prolines are favoured in short rigid loops/turns

loops at the end of domains are important for binding to things

what are motifs? what are examples?

repeated sections in a protein

sequence motifs: PXXP or NXS/T
structural motifs: beta-alpha-beta or helix-turn-helix

details on tertiary structure

soluble proteins fold into compact structures with nonpolar cores (with the exception of membrane proteins)

core of protein is hydrophobic

tertiary can be part of a protein (single chain), or the final structure of the protein. can be single or multiple domains

what is the exception of hydrophobic core of protein

membrane proteins core is hydrophilic, because they are in the membrane, their outside is covered in lipids (hydrophobic), and need to keep the inside polar (hydrophilic) environment

what type of interaction would dominate proteins coming together?

you would think hydrogen bonding, but it’s actually van der waals interactions

VDW are small in terms of energy, but entropy and the effect on water plays a major role in proteins interacting

hydrophobic interactions don’t like to be near water, they repel water, and that entropy drives the interaction, this is the VDW forces

what are quaternary structure

polypeptide chains assembled into multi-subunit structures

not all proteins have this structure

details on hydrophobicity/hydrophilicity of amino acids

nonpolar side chains interact poorly with water, tend to become buried away from aqueous solvent

polar/charged side chains interact favourably with water through H-bonds and ion-dipole interactions