Exam I Study Guide
Supplement
Molecular Chaperons and Protein Folding
Answer/discuss one or more of the following questions/statements:
- What is the function of the chaperons?
- To prevent inappropriate folding, thus aiding proper folding to the native state, and/or
- To create an environment allowing improperly folded or denatured proteins to refold to a native conformation.
- What are the different types of chaperones (describe) and how do their functions differ?
- Ribosome Biinding: TF, DnaK, DnaJ (and eukaryotic analogs)—stabilize nacent chains n a state poised for rapid folding.
- Hsp70 system: bind and release, with the use of ATP, extended peptide segments in non-native conformations.
- Prefoldin (PFD): exposed hydrophobic residues bind and release denatured protein regions, stabilizes nascent peptide chains for transfer to chaperonins.
- Chaperonins: large barrel shaped multisubunit proteins that provide and enclosed space where a non-native protein and open and refold to a native conformation.
- Why might protein aggregation be a major problem for cells without chaperons?
- Generally the cell is so crowded with proteins etc. that it is difficult for proteins to fold without interference.
- How do Chaperones prevent aggregation?
- By transiently binding to exposed hydrophobic residues and/or by isolating non-folded proteins from the cytosol.
- Follow-up on one of the more open questions below:
- Is the existence of chaperons, and their necessity in many cases, consistent with the idea that ALL of the folding information for proteins is in the primary sequence?
- Yes, current theories/models of chaperon actions DO NOT involve the chaperons as active participants in folding, merely as mechanisms to allow proper folding in a challenging environment.
- Reconcile (or refute) the fact that chaperonins require ATP energy for their activity with the statement that proteins "self-assemble."
- Current models of ATP use see it in a number of possible actions that enable self-assembly:
- first, ATP energy can be used to “open & close” the chaperone, allowing non-native proteins into an enclosed space,
- second, ATP energy can be used to change the chaperone conformation to favor binding or release of unfolded peptide regions.
- third, ATP energy could be used to unfold badly folded proteins, enabling them to refold spontaneously to a native state.
- None of these uses involve ATP as a driver of folding.
- Is the suggestion of co-translational domain folding consistent with a requirement for chaperons? Explain.
- Co-translational folding allows domains to fold as they are formed, but chaperones may still be required to aid the domains to come together into the final structure. They may also be involved in aiding there domain level folding at the ribosome.
Last modified 24 February 2012