Biochem - Lecture 5 Learning Objectives

all of the learning objectives for the 5th lecture about tertiary and quaternary structures and protein folding

amphipathic alpha helix

an alpha helix with opposing polar and nonpolar faces that are oriented along the helix's long axis

tertiary structure

all aspects of a 3-D folding of peptide chains

quaternary strutcure

arrangement in space of 2 or more polypeptides

motif

short, conserved sequence of amino acids that are important for protein function

domain

structurally independent folding units with distinct tertiary structures but are all a part of the same polypeptide chain

what are the 3 principles guiding folding of water-soluble globular proteins?

1. minimization of solvent-accessible surface area

2. maximization of Hydrogen bonding within a protein

3. chiral effect

what is minimization of solvent-accessible surface area?

burying as many hydrophobic groups as possible within the protein to decrease the amount of them touching the water

what is maximization of hydrogen bonding within a protein?

polar backbone groups and side chains tend to be either in contact with water or hydrogen bonding with other protein groups in order to maximize the amount of hydrogen bonding

what is the chiral affect?

the tendency of extended backbone structural arrangements to be right-handed as a result of having all L configuration amino acids

beta alpha beta loop

protein that is a beta conformation connected to an alpha helix connected to a beta conformation, all connected by loops

beta barrel

beta conformation wraps around

how many domains are in this protein?

2

how many domains in this protein?

4

myoglobin structure

made of 70% alpha helices, with the remaining 30% being mostly turns and loops, with no beta sheets or conformations at all

immunoglobulin structure

this is made up of entirely beta strands with loops and no alpha helixes. Has 4 domains

immunoglobulin fold

a protein domain that is made up of two antiparallel beta sheets

alpha beta barrel protein

parallel 8-stranded beta barrel on interior, surrounded by alpha helices

structure of globular protein embedded in lipid bilayer

hydrophobic residues are on the outside and hydrophilic on the inside, creating a channel for water to pass through

subunit

each polypeptide in a multichain protein

rotational axis of symmetry

an imaginary line through a molecule where, if rotated by a specific angle (360°), the molecule appears identical to its original structure

denaturation

unfolding or breaking of a protein

renaturation

process of restoring a denatured protein

homometric

has identical subuinits

heterometric

has different subunits

2-fold symmetry

if you rotate 180° about the axis, the protein will look as though it never moved

3-fold symmetry

if you rotate 120° about the axis, the protein will look as though it never moved

delta G folding

change in free energy between unfolded structure and folded structure

is the delta G folding large or small between the unfolded structure and the folded structure?

very small

loss of 1 or 2 hydrogen bonds might do what to equilibrium of a protein?

it might shift equilibrium from folded state to unfolded state

is the folded form of a protein in a higher
or lower free energy state than the unfolded state?

lower free energy state, meaning it is more stable and energetically favorable

what four things contribute to enthalpy change in folding?

1. electrostatic effects

2. solvation/desolvation of charged residues

3. Van der Waals interactions

4. steric factors

what two things contribute to entropy change in folding?

1. hydrophobic effect

2. conformational entropy

what is conformational entropy?

a major force that opposes protein folding, it is defined as the entropy associated with the number of conformations that a molecule has

is entropy lost or gained due to the conformational entropy?

entropy is lost due to the molecules having less ability to move around (meaning less disorder)

what is the affect of beta-mercaptoethanol on proteins?

it reduces the disulfide bonds in a protein (reducing agent)

what is the affect of urea on proteins?

urea is a denaturing agent, so it disrupts the noncovalent bonds within the protein that stabilize its structures (structures become be stabilized)

what was Anfinsen’s experiment?

he took denatured ribonuclease (RNase) and in one experiment he removed the urea and then oxidized it. In the other he first oxidized the RNase, then he removed the urea

what did Anfinsen find in his experiment?

he found that if you remove urea first and then oxidize it, you still get fully active RNase, but if you reverse the process and oxidize it and then remove the urea, you do not get active RNase

what was the general conclusion drawn from Anfinsen’s experiment?

the native tertiary structure is determined entirely by the primary structure of a protein and is most stable under native (physiological) conditions

cross-beta structure

protein strands are aligned side by side and form hydrogen bonds to create a stable sheet-like structure that is characteristic in many proteins that misfold

what do cross-beta structures lead to the formation of?

amyloid plaques

amyloid plaques

built up clumps of proteins in the brainwha

what disease can cross-beta structures and amyloid plaques cause?

Alzheimer disease

what is the name of the peptide that aggregates extracellularly in Alzheimer disease?

amyloid-beta peptide

what is the name of the protein that’s the source of the peptide that aggregates extracellularly in Alzheimer diease?

amyloid-beta precursor protein (APP)

what is the general type of secondary structure of the aggregate in the amyloid fibers?

beta sheet structure