KH4 Flashcards
Explain why eggs are solid when cooked?
Heating denatures their proteins and when they refold, there are exposed hydrophobic patches that interact together (aggregation)
True or False? “Proteins fold randomly, without following a specific pathway”
False. Local interactions create folds which complexify over time. Eventually, it all collapses together.
True or False? “Protein chains start to fold once they’re completely synthesized”
False. The N terminus (start) begins folding as the C terminus (end) is created (or sooner).
What are chaperones? What do they do?
They’re proteins that guide the folding of other proteins by recognizing exposed hydrophobic patches. (ATP-dependent cycle, bind and release, block exposed patches)
True or False? “Chaperones are upregulated under conditions that accumulate misfolded proteins”
True
What are five specific functions of chaperones?
fold newly proteins // refold misfolded proteins // disassemble toxic aggregates // assembly and disassembly of multiprotein complexes // mediate transformations between active and inactive forms
What are the two chaperone classes? What’s the difference between the two?
Molecular chaperones (work alone) and Chaperonins (forms multisubunit chamber)
Why are many chaperones called “Hsp”?
They were discovered under conditions that denature proteins: heat shock.
How do Hsp60s (chaperonins) work?
They form an enclosed chamber made of protein-binding subunits. These subunits change shape through either ATP-binding and hydrolysis (1) or their own motion (2). Inside the correct conformation, the protein gets reshaped.
Can chaperones be used for evolutionary research?
Since most proteins rely on them to fold properly, they’re essential to life. Thus, they’re highly conserved in evolution.
Assuming chaperones aren’t present, what happens to misfolded proteins?
They are degraded through proteolytic cleavage.
Describe the proteolytic cleavage process.
Poly-ubiquitin latches onto damaged and misfolded proteins. These tagged proteins are fed into a multisubunit chambre (the inside of which has proteases).
During proteolytic cleavage, how are poly-ubiquitin tags created?
E1 bonds to Ub and passes it to E2. E3 recognizes misfolded proteins and tells E2 to pass it the Ub. Eventually, a chain of Ub is formed.
How do proteasome destroy misfolded proteins?
Recognize the Ub tag and removes it. Binds the protein and misfolds it before cleaving it into smaller peptides (which it then releases).
How do E3 ubiquitin ligases know what proteins to target?
They recognize exposed hydrophobic patches and oxidized amino acids.
