An Hsp90 physical interactome

Hsp90 is a critical eukaryotic molecular chaperone, ubiquitously expressed in all organisms. It is a highly abundant protein (~2% of a cell’s protein mass) and is involved in numerous processes including protein trafficking, chromatin remodeling, and signal transduction. To govern a broad variety of biological pathways Hsp90 exploits two different modes of interactions with clients and/or co-chaperones - a stable association such as when maintaining a metastable client in a soluble state and a transient binding such as when driving the dynamics of proteins working in transcription, chromatin remodeling, or DNA repair. Despite the numerous and extensive studies on Hsp90, the complete clientele of Hsp90 is unknown. Likely, the transient interactions between Hsp90 and many of its clients make their identification through traditional techniques difficult. To gain a better understanding of the factors interacting with Hsp90, I exploited the non-natural amino acid p-Benzoyl-L-Phenylalanine (Bpa) to generate an in vivo kinetic trap to capture Hsp90 interactions. In conjunction with mass spectrometry, I have identified 1114 physical interactors of Hsp90. Nearly half of the hits were novel for Hsp90-association and included pathways such as translation initiation and genome organization. My studies provide mechanistic insights into Hsp90 as a molecular chaperone as well as its functional role in different cellular processes.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Cell and Developmental Biology

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2022

Author dc:creator

• Kolhe, Janhavi Atit

Contributors dc:contributor

• Freeman, Brian C
• Brieher, William M
• Raetzman, Lori T
• Li, Xin

• Hsp90
• Molecular Chaperone
• Bpa Crosslinking

Statement dc:rights

• Copyright 2022 Janhavi Kolhe

Language dc:language

en, eng

Handle dc:identifier

https://hdl.handle.net/2142/117785

OAI record oai:identifier

https://www.ideals.illinois.edu/oai-pmh?verb=GetRecord&metadataPrefix=etdms&identifier=oai%3Awww.ideals.illinois.edu%3A2142%2F117785