GENE 500 Lecture Notes - Lecture 4: Energy Landscape, Protein Folding, RibonucleasePremium

3 pages85 viewsFall 2018

School

Department

Genetics

Course Code

GENE 500

Professor

Lawrence Grossman

Lecture

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Lecture 4 - Number of Proteins

Correcting Misfolded Proteins

• Although a small protein like ribonuclease

can fold spontaneously, even it is slow by

biological standards

• In the cell, protein folding is assisted by

chaperones and chaperonins

• Chaperones help move proteins to and

between energy states

• Energy landscape limited by co-translation

• Solvent is part of the process; in aqueous

medium, hydrophobic residues form the internal

core

Step 1: When bound to ATP, the monomeric

Hsp70 protein assumes an open conformation, in

which an exposed hydrophobic substrate-binding

pocket transiently binds to exposed hydrophobic

regions of an incompletely folded or partially

denatured target protein, and then rapidly

releases this substrate, as long as ATP is bound

Step 2 & 3: Hydrolysis of the bound ATP causes the molecular chaperone to assume a closed

form that binds its substrate protein much more tightly, and this tighter binding appears to

facilitate the target protein’s folding, in part by preventing it from aggregating with other

unfolded proteins; induces a large conformational change in the substrate-binding domain,

resulting in the closed conformation, in which the substrate is locked into the substrate-binding

domain; here proper folding is facilitated

Step 4 & 5: Exchange of ATP for the bound ADP, stimulated by other accessory cochaperone

proteins (GrpE/BAG1), converts the Hsp70 back to the open conformation, releasing the

properly folded substrate and regenerating the open conformation, which can then interact

with additional substrates

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