KH4 Flashcards
What is the structure of properly folded proteins
Hydrophobic amino acid side chains are not exposed at the surface but are buried in the core
What is a general sign of misfiling
Hydrophobic patches at the surface of a protein
What does in vitro conversion between native and denatured conformations show
Native conformation can be denatured (with urea) and renatured which shows that 3D structure is determined by amino acid sequence
Characteristics of misfiled proteins
- wrong conformation
- Insoluble
- Aggregation irreversible
Which region folds first N or C terminus
N-terminus
How is spontaneous refilling of a denatured protein through t to be through
A folding pathway
What are chaperones and what are their functions
Proteins that help guide protein folding along productive pathways by permitting partially misfolded proteins to return to the proper folding pathway
Where can chaperones be upregulated
Under conditions where misfolded proteins accumulate (ex: heat shock induced proteins)
What are examples of functions of chaperones
- Can fold newly made proteins into functional conformations
- Refold misfolded or unfolded proteins into functional conformations
- Disassemble potentially toxic protein aggregates that form due to protein misfolding
- Assemble and disassemble large multi protein complexes
- Mediate transformations between inactive and active forms of some proteins (changing shape)
How do chaperones work
Work through ATP-dependent cycles of binding to, and release from misfolded client molecules at exposed hydrophobic patches
How does blocking the exposed hydrophobic patches help
The chaperones can keep folding or refolding protein out of trouble while productive folding events occur (protect from aggregation until properly folded)
What are the two major classes of chaperones
- Molecular chaperones (operate as single molecules)
- Chaperonins (form a multi subunit refolding chamber)
Structure of chaperonins
Form and enclosed chamber made up of inward-facing protein binding subunits that undergo concerted ATP-binding/hydrolysis and conformation change
How many proteins make up the quaternary structure of chaperonins
7 with a chamber inside (where refolding occurs)
What are the groups of chaperonins
Group 1: removable cap
Group 2: no removable cap, lip and conformational change
Why are chaperonins/chaperones essential to life
The majority of cellular proteins require the assistance of chaperonins/chaperones to adopt their 3D structures during synthesis or to properly refold if misfolded
Chaperonin/chaperone evolution characteristics
Ancient, very highly conserved in amino acid sequence through evolution
What happens w=if chaperones/chaperonins can’t correct the misfolding
Proteins are destroyed by proteolytic cleavage into small fragments
What are chaperones most likely to recognize
Exposed hydrophobic patches
What are the steps for ubiquitin/proteasome system for protein degradation
Step 1: Poly-ubiquitin tags damaged or misfolded proteins for degradation
Step 2: Ubiquitin-tagged proteins are fed into a multi subunit chamber in which the subunits form inward-facing proteases
What is ubiquitin and what can it do
A 76-residue protein that can be covalently linked to lysine residues on target proteins
What compounds are involved in step 1 of the ubiquitin/proteasome system for protein degradation
E1: ubiquitin activating enzyme
E2: Ubiquitin-conjugating enzyme
E3: Ubiquitin ligand
Ubiquitin
What is the function of E1 and E2
Takes ubiquitin, hydrolyzes ATP and uses energy to attach ub to itself on C-terminal
What is the function of E3
Recognizes the protein that should be destroyed, targets misfolded proteins (recognize exposed hydrophobic patches)
