Module 4: Protein folding Flashcards
phi
angle b/w N and alpha-C
Psi
angle b/w alpha-C and carbonyl
Ramachandran plot
visualize which combo of phi, psi, angles are statically allowed in protein structure
Alpha Helix
coil
R groups protrude outward
single turn: 3.6 residues/turn
stabilized by HBs b/w H attached to N atom of peptide linkage and carbonyl of fourth aa on amino terminal side
results in all amide groups pointing to N-terminal and all carbonyl pointing to C terminal
What aa is most likely to form an alpha helix?
alanine
Beta sheet
formed by single beta strands lined up side-by-side (either antiparallel/parallel)
held by HBs -carbonyl O of one beta sheet H-bonded to H attached to amine on adjacent beta sheet)
Once pr- folded, what happens to entropy?
First, entropy decreases
- primary structures would be surrounded by rotationally constrained water molecules (fewer conformations=lower entropy)
Upon protein folding a lot of the hydrophobic residues are buried in the protein core and are interacting with one another-water released/free to tumble around=increase in entropy
Motif
recognizable folding pattern involving two or more elements of secondary structure and the connection(s) between them
Domain
part of a polypeptide chain that is independently stable or could undergo movements as a single entity with respect to the entire protein
typically large pr-
Fibrous Protein
structural roles in cells/tissue
elongated/filamentous in shape
collagen/keratin=long-lasting, resistant to degradation/modification
Globular Protein
carry out synthesis, transport, metabolism
very compact structures
bury hydrophobic aa in core and hydrophilic/polar aa on surface
Membrane Proteins
use high hydrophobic aa area to interact w hydrophobic acyl chains of lipid bilayer
- rest on top of bilayer (peripheral membrane pr-)/fully integrated (integral membrane pr-)
Electrostatic forces
strong
charge-charge
long distance interactions
strength can be weakened on surface of pr- due to water and its larger dielectric constant
Hydrogen bonds
usually occur b/w peptide groups and water on pr- surface
in pr- core, occurs b/w peptide groups
highly directional
Van der Waals
short interaction range (almost in contact)
very influential when lots
also have corresponding repulsive forces
Hydrophobic effect
hydrophobic groups have tendency to cluster together in pr- interior to exclude water
hydrophobic group in water reduces # of HBs free water mol make=thermo unfavourable
thus, water becomes more ordered around hydrophobic mol to conserve HBs and decrease entropy=energetically unfavourable
Cooperativity
Pr- highly cooperative w respect to folding
Collagen
about 1/4 of all pr-, structural pr-
strengthens tendons and support skin and internal organs
composed of 3 chains in tight triple helix
over 1400 aa long
Hemoglobin
composed of 2 alpha chains and 2 beta chains -each w ring-like heme group containing iron
once 1 heme bind oxygen, it nudges neighbours to change shape making them more susceptible to bind oxygen
Myoglobin
small, bright red pr-
common in muscle cells
stores oxygen for muscles
contains heme group
ATP Synthase
composed of two rotary motors: F0 (electric motor) embedded in membrane and F1 (chemical motor) powered by ATP
F0 motor uses the power from a proton gradient to force the F1 motor to generate ATP
F1 structure
uses the power of rotational motion to build ATP, or when operating as a motor, it breaks down ATP to spin the axle the opposite direction
synthesis of ATP: binding of ADP and phosphate, the formation of the new phosphate-phosphate bond, and release of ATP (diff conformations for each step)
F0 structure
rotor is composed of 12 identical protein chains
pump has an arginine amino acid that hands off a hydrogen ion to aspartates on the rotor
Insulin Receptor
When blood glucose levels rise, beta cells in the pancreas release insulin=uptake of glucose
large protein that binds to insulin and passes its message into the cell
have two tyrosine kinases: when insulin not present, held in a constrained position, but when insulin binds, these constraints are released
Type I diabetes vs type II
Type I: pancreatic cells that produce insulin are destroyed by autoimmunity, or insulin is mutated and inactive
Type II: acquired resistance to the action of insulin on its receptor
