Mechanistic studies of the ClpAP protease/

CIpA, a member of the Hspl00/Clp subset of the AAA+ superfamily, is an energy-dependent chaperone, disassembling and remodeling its protein substrates. CIpA also serves as the ATPase component of the ClpAP protease, where it is resonsible for binding specific substrates and unfolding and translocating them into its partner ClpP, the proteolytic component of the complex. We have used single molecule and traditional biochemical experiments to probe the mechanism of the unfolding and translocation steps of ClpA's enzymatic activity. We have identified two states of varying substrate affinities and shown that the conformational switch between these states is responsible for protein translocation. We have also investigated ClpA's autounfolding activity and have demonstrated that though CIpA can disaggregate some substrates in vivo, it does not act as an autodisaggregase.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Chemistry.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2008

Author dc:creator

• Farbman, Mary E

Advisor dc:contributor.advisor

• Stuart Licht.

• Chemistry.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/46048

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/46048