1. 3.12-3.13 Proteins – Pt. 2: Protein Folding Pg. 43-45 Objective: 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.

2.  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

3.  Enzymes (folded, functioning protein) have an active site: 3-D space/groove (shape) ▪Where molecules attach to be catalyzed

4.  What determines shape of protein?  Location of folds – where folds occur ▪What determines where folds occur? ▪Sequence of A.A. (primary structure) Why? How?

5.  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…

6.  Proteins unfold because…  Increase temperature: heat  moves  break  Change pH: H + /OH - wants more than δ + /δ - (polarity)  Both affect/break H-bonds  How?

7.  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

8. 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…

9.  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

10.  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://folding.stanford.edu/  http://fold.it/portal/ http://fold.it/portal/

11.  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