Chapter 4 - Protein Structure

proteins are made of…

≥1 polypeptides (chains of amino acids)

structure and charges of amino acids at physiological pH

isolated amino acid has both a positive and negative charge

formal name of isolated amino acide

alpha amino acids, because central carbon is alpha carbon

number of amino acids, how they’re grouped

20, grouped by properties of R groups → hydrophobic, polar, charged (and one nonpolar)

hydrophobic amino acids

alanine, phenylalanine, leucine, isoleucine, methionine, valine, tryptophan, proline

polar amino acids

serine, threonine, tyrosine, cysteine, asparagine, glutamine, histidine

charged amino acids

aspartate, glutamate, lysine, arginine

weird nonpolar amino acid

glycine → R group is hydrogen, so it’s not polar or hydrophobic or charged

chirality of amino acids

all but glycine are chiral (19/20)

chiral form of amino acids found in proteins

form on the left

amino acid with no chirality

glycine

formation of peptide bond, what it looks like

reaction in which amino acids are linked

condensation reaction, where water is removed (from amino and carboxylic acid groups)

two ways peptide bonds can be broken

hydrolysis via exopeptidases or endopeptidases (enzymes that cut peptides)

exopeptidases act upon/cut peptides…

at the end of polypeptide chain

endopeptidases act upon/cut peptides…

from the middle of the polypeptide chain

which is the N-terminus of polypeptide

the end with amino group; beginning of the chain (first formed)

which is the C-terminus of polypeptide

the end with carboxylic acid; end of the chain (last formed, last to leave ribosome)

how to tell charge for a specific amino acid or N/C terminus given pH?

If pK of aa/terminus < pH, will be deprotonated from. If pK of aa/terminus > pH, will be protonated form. If you want the charge of the entire polypeptide at a certain pH, find the charge for each aa, N terminus, and C terminus, and add them together.

how many of the 20 amino acids are found in each protein, usually?

all 20

primary structure of protein

sequence of amino acids

secondary structure of proteins

conformation of polypeptide backbone, not taking side chains into account (how backbone folds - 2D structure)

tertiary structure of proteins

3D conformation of folded polypeptide - how the backbone and side chains fold/interact

quaternary structure of proteins

spatial arrangement and interaction of multiple polypeptides in proteins containing more than one polypeptide chain

conformation/rotation of peptide bonds

there is no rotation around the C-N bond!

Regular secondary structures

alpha helices & beta sheets → repeating conformations of polypeptide backbone

why are alpha helices and beta sheets so common?

they are stabilized by hydrogen bonds

typical length of alpha helices

~10 amino acid residues

parallel beta sheets

all N-terminuses and C-terminuses are aligned; polypeptide chains are aligned in the same direction

antiparallel beta sheets

N-terminuses and C-terminuses alternate on each side of the beta sheet; polypeptide chains are aligned in opposite directions

typical structure of globular proteins

hydrophobic core (often called domain) and hydrophilic surface

largest force governing protein structure

hydrophobic effect

other common forces holding together protein structure (not hydrophobic effect)

ion pairs, interactions with zinc ions, disulfide bonds, thioester bonds, isopeptide bonds

relative chronology of protein structure development

hydrophobic collapse is first → hydrophobic residues to center, hydrophilic residues to surface

next is development of secondary structures like alpha helices and beta sheets → they DO NOT form immediately

molecules helping with protein folding

chaperone proteins

traits of all/most proteins

inherently flexible, often containing some level of disorder

monomorphic proteins

only have a single stable tertiary structure

metamorphic proteins

have two or more possible tertiary conformations

intrinsically disordered proteins

have no fixed structure → primary structure remains the same, but secondary/tertiary are variable

relative energy/stability of monomorphic, metamorphic, and intrinsically disordered proteins

IDPs least stable/highest amount of free energy, then metamorphic, and monomorphic proteins have the lowest free energy/most stability

intrinsically disordered regions

regions with no particular secondary/tertiary structure in a protein; the protein may have both stable regions and IDRs (different than IDP, where entire protein’s structure is variable)

common functions of IDRs

as linkers/spacers, like ‘hinge’ regions connecting antibody proteins’ domains

perform like molecular springs

may wrap around and solubilize calcium phosphate → essential for biomineralization

aggregate in tangled network undergoing liquid-liquid phase separation

liquid-liquid phase separation

IDRs aggregate and separate from liquid environment, though remaining in a liquid state (more gel-like) → this aggregate is protein-rich and sometimes called a membraneless organelle

subunits in a protein

each individual polypeptide chain (since proteins are typically made of multiple)

general name of proteins if same subunits

homodimer, homotrimer, homotetramer… homo prefix with suffix of number of subunits

general name of proteins if different subunits (not all the same, even if like 2/4 are the same)

heterodimer, heterotrimer, heterotetramet… hetero prefix with suffix of number of subunits

polypeptides’ spatial arrangement is known as…

protein quaternary structure

some diseases characterized by misfolded protein aggregates

Alzheimer’s, Parkinson’s, TSEs (transmissable spongiform encephalopathies) (these are neurodegenerative disease)

amyloid deposits

aggregates of misfolded proteins → different types for each disease

name comes from amyloids’ starch-like appearance

most toxic form of amyloid-beta

the dimer