Publication:
Components of a Protein Machine: Allosteric Domain Assembly and a Disordered C-terminus Enable the Chaperone Functions of Hsp70

Simple item page
dc.contributor.advisorLila Gierasch
dc.contributor.advisorCraig Martin
dc.contributor.advisorJeanne Hardy
dc.contributor.authorSmock, Robert G
dc.contributor.departmentUniversity of Massachusetts Amherst
dc.date2023-09-23T04:50:20.000
dc.date.accessioned2024-04-26T19:49:42Z
dc.date.available2024-04-26T19:49:42Z
dc.date.issued2011-09-01
dc.description.abstractHsp70 molecular chaperones protect proteins from aggregation, assist in their native structure formation, and regulate stress responses in the cell. A mechanistic understanding of Hsp70 function will be necessary to explain its physiological roles and guide the therapeutic modulation of various disease states. To this end, several fundamental features of the Hsp70 structure-function relationship are investigated. The central component of Hsp70 chaperone function is its capacity for allosteric signaling between structural domains and tunable binding of misfolded protein substrates. In order to identify a cooperative network of sites that mediates interdomain allostery within Hsp70, a mutational correlation analysis is performed using genetic data. Evolutionarily correlations that describe an allosteric network are validated by examining roles for implicated sites in cellular fitness and molecular function. In a second component of the Hsp70 molecular mechanism, a novel function is discovered for the disordered C-terminal tail. This region of the protein enhances the refolding efficiency of substrate proteins independently of interdomain allostery and is required in the cell upon depletion of compensatory chaperones, suggesting a previously undescribed mode of chaperone action. Finally, experiments are initiated to assess the dynamic assembly of Hsp70 domains in various allosteric states and how domain orientations may be guided through interaction with partner co-chaperone proteins.
dc.description.degreeDoctor of Philosophy (PhD)
dc.description.departmentMolecular and Cellular Biology
dc.identifier.doihttps://doi.org/10.7275/2389184
dc.identifier.urihttps://hdl.handle.net/20.500.14394/38893
dc.relation.urlhttps://scholarworks.umass.edu/cgi/viewcontent.cgi?article=1456&context=open_access_dissertations&unstamped=1
dc.source.statuspublished
dc.subjectAllostery
dc.subjectDnaK
dc.subjectHsp70
dc.subjectIntrinsic disorder
dc.subjectMolecular chaperone
dc.subjectProtein folding
dc.subjectCell Biology
dc.titleComponents of a Protein Machine: Allosteric Domain Assembly and a Disordered C-terminus Enable the Chaperone Functions of Hsp70
dc.typedissertation
dc.typearticle
dc.typedissertation
digcom.contributor.authorisAuthorOfPublication|email:rsmock@student.umass.edu|institution:University of Massachusetts Amherst|Smock, Robert G
digcom.identifieropen_access_dissertations/447
digcom.identifier.contextkey2389184
digcom.identifier.submissionpathopen_access_dissertations/447
dspace.entity.typePublication
Files
Original bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
Smock_umass_0118D_10835.pdf
Size:
24.41 MB
Format:
Adobe Portable Document Format
Name: Smock_umass_0118D_10835.pdf
Size: 24.41 MB
Kind: Adobe PDF
Collections
Dissertations