Protein Structure and Function 2 (L4) Flashcards
native state
protein folds into the most stable position (lowest free energy)
why are proteins not always in their native states inside the cell?
- multiple stable conformations
- pH
- need chaperones for folding
- not enough space inside cell
purpose of chaperones/chaperonins
assist in protein folding - creates isolated compartment for protein to fold properly
chaperones
HSP
chaperonins
GroEL, GroES -> cylindrical macromolecular complex
Alzheimer’s disease
abnormal protein folding -> amyloid plaques that are insoluble protein aggregates
amyloidogenic vs. non-amyloidogenic protein products
amyloidogenic: A-beta-42 pieces aggregate w/ each other
non-amyloidogenic: A-beta-40 pieces that are relatively soluble (not a problem)
A-beta normal vs. pathologic
normal: usually have alpha helices
path: more beta sheets that are more hydrophobic - fall out of solution and aggregate -> amyloid plaque
two classical pathological hallmarks of Alzheimer’s
neurofibrillary tangles (protein aggregates inside neurons) and amyloid plaques
concept of specificity
does protein bind only one thing or does it bind many things
concept of affinity
how tightly a protein binds its substrate
relationship b/w kd and affinity
high kd -> more dissociation -> low affinity
low kd -> less dissociation -> high affinity
what is an example of binding that is usually very tight and specific?
antibody-antigen (complementarity-determining regions)
antibody generation in B cells
somatic recombination then somatic hypermutation
somatic recombination
different combinations for binding w/ particular antigens
somatic hypermutation
evolved a way to create new mutations:
- deamination
- mismatch w/ error prone DNA pol -> more new lesions
- activation-induced deaminase: base-excision repair w/ low fidelity DNA pol delta -> create more mutations that generate variety in antibodies to bind more antigens