Mechanism of BiP and Grp94 Coordination by a J-protein Cochaperone

DSpace Repository

Show simple item record

dc.contributor.advisor Street, Timothy Nguyen, My Anh 2020-05-26T13:13:10Z 2020-05-26T13:13:10Z 2020
dc.description.abstract To prevent protein aggregation in cells, molecular chaperones stabilize non-native conformations of substrate (“client”) proteins and facilitate their correct folding. Clients often interact with chaperones in a defined order, but the mechanisms that enable coordinated interactions of clients with chaperones are poorly understood. One such case is the Hsp70 and Hsp90 families of chaperones in which clients are transferred from Hsp70 to Hsp90. This study focuses on the Hsp70/Hsp90 paralogs in the endoplasmic reticulum (BiP/Grp94) and uncovers the role of a BiP co-chaperone (ERdj3) in facilitating the sequential interactions of client proteins first with BiP, and then with Grp94. In the first part of my thesis, I show that the Erdj3 J-domain (JD) selectively binds the ATP conformation of BiP and subsequently drives BiP into the ADP conformation by stimulating BiP ATP hydrolysis. I develop a quantitative model that explains the influence of the JD on BiP ATPase activity and conformation. In the second part, I show that the JD/BiP interaction mechanism enables a well-defined sequence of chaperone interactions with BiP/JD coming first and Grp94/BiP coming second. Finally, I discover that phosphate release from BiP after ATP hydrolysis plays an important role for conformation of BiP and also for the coupling of BiP to Grp94.
dc.format.mimetype application/pdf
dc.language English
dc.language.iso eng
dc.publisher Brandeis University
dc.relation.ispartofseries Brandeis University Theses and Dissertations
dc.rights Copyright by MyAnh Nguyen 2020
dc.subject BiP
dc.subject Grp94
dc.subject heat shock protein 90 (Hsp90)
dc.subject ERdj3
dc.subject J-protein cochaperone (Hsp40)
dc.subject foster resonance energy transfer (FRET)
dc.subject fluorescence anisotropy
dc.subject structural dynamics
dc.title Mechanism of BiP and Grp94 Coordination by a J-protein Cochaperone
dc.type Thesis
dc.contributor.department Department of Biochemistry MS Masters Biochemistry Brandeis University, Graduate School of Arts and Sciences
dc.description.esploro 2

Files in this item

This item appears in the following Collection(s)

Show simple item record

Search BIR


My Account