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