Chapter 3: Molecules of Life3.12-3.13 Proteins – Pt. 2: Protein FoldingPg. 43-45Objective: I can describe and explain how the folding of a protein determines its ability to function and errors in this can result in various diseases/disorders.

Quick Review of Yesterday (Tue)! (feel free to look @ notes)

Primary Structure = sequence of amino acids (20 types can be linked in any order)

Secondary Structure = bends/twists in chain Caused by (mostly) hydrogen bonds 2 types = α-helix & β-sheets

Tertiary Structure = overall shape of 1 polypeptide chain (from all bends/twists) Caused by cross-linking, “hydrophobic hiding”

Quaternary Structure = overall structure of several polypeptide chains functioning protein

Primary Structure Determines All Other Levels

Protein Shape (4th) is Important!

Enzymes (folded, functioning protein) have

an active site: 3-D space/groove (shape)▪ Where molecules attach to be catalyzed

Proteins come in large variety of shapes

What determines shape of protein? Location of folds – where folds occur

▪ What determines where folds occur?▪ Sequence of A.A. (primary structure)

Why?

How?

Protein Folding

Proteins fold because…(review)

Polar A.A. attract (H-bonds may form) Nonpolar A.A. repel watery environment Cross-linking from “special” A.A. (Sulfur)

Folded proteins can perform function Has 3-D shape shape provides function

▪ If unfolded…

Denaturation: Protein unfolding

Proteins unfold because… Increase temperature: heat moves break

Change pH: H+/OH- wants more than δ+/δ- (polarity) Both affect/break H-bonds

How?

Chaperone Proteins a.k.a. Chaperonins

Proteins (enzymes) can fold in MANY ways But need to have right shape to do function! Chaperonins can help new proteins fold correctly by isolating from environment

Chaperone Proteins a.k.a. chaperonins

Some chaperonins are heat-shock proteins Will help protein refold after

high temperature denature

Not always possible to “renature” back into right shape…

Protein Folding Problem

Know sequence of MANY proteins= Do not know the conformation (structure/shape)

When protein folded incorrectly, may lead to many diseases (often due to incorrect sequence primary): Sickle-cell anemia, Cystic fibrosis, Alzheimer’s,

Huntington’s, Parkinson’s, and several cancers

Prions – group of diseases where misfolded protein causes good, normal protein to misfold & malfunction Mad Cow’s Disease, Kuru (most affect the brain)

Primary structure

Secondary, Tertiary, Quaternary structure

Protein Folding & Curing Disease Because many diseases caused by proteins

folded incorrectly, if can figure out correct way to fold, maybe can cure disesase

Programs to figure out how proteins fold http://folding.stanford.edu/ http://fold.it/portal/

Summary of Protein Folding

If denatures (unfolds) = bad No shape, no function (heat, pH change) Usually, death

If fold the wrong way = bad Does not perform proper function May misfunction disease

If fold wrong way AND cause other good proteins to misfold = bad Prions = special disease