Fields of Research
- Molecular Basis of Disease
- Protein Structure
Research Summary
Mechanisms of proteostasis as carried out by protein ubiquitylation and protein chaperones
Research Statement
The Klevit lab is interested in understanding how cells deal with stress and regulate cellular function at a fundamental and atomic level. As structural biochemists, we leverage an ever-expanding toolkit of structural techniques including NMR, x-ray crystallography, cryo-EM, HDXMS, XLMS and biochemical/molecular biological techniques to discover how proteins perform critical functions. We focus on two main processes: protein ubiquitylation and protein chaperones. Some of our current molecular of interest are: BRCA1/BARD1, HHARI, HSPB1, HSPB5, and tau.
Awards and Honors
Rachel Klevit
Professor of Biochemistry; Adj. Prof. of Pharmacology; Adj. Prof. of Chemistry
Affiliations
UW Graduate Programs: Biochemistry, Pharmacology, BPSD, MCB
UW/FHCRC Cancer Consortium
Rachel Klevit
Professor of Biochemistry; Adj. Prof. of Pharmacology; Adj. Prof. of Chemistry
Affiliations
UW Graduate Programs: Biochemistry, Pharmacology, BPSD, MCB
UW/FHCRC Cancer Consortium
Faculty
- Building:
- Health Sciences Building
- Room:
- K-466
- Box:
- 357350
- Phone:
- 206-543-5891
Lab
- Building:
- Health Sciences Building
- Room:
- K-464
- Box:
- 357350
- Phone:
- 206-543-6391
Rachel Klevit
Professor of Biochemistry; Adj. Prof. of Pharmacology; Adj. Prof. of Chemistry
Affiliations
UW Graduate Programs: Biochemistry, Pharmacology, BPSD, MCB
UW/FHCRC Cancer Consortium
BIOC 530
Rachel Klevit
Professor of Biochemistry; Adj. Prof. of Pharmacology; Adj. Prof. of Chemistry
Affiliations
UW Graduate Programs: Biochemistry, Pharmacology, BPSD, MCB
UW/FHCRC Cancer Consortium
Rachel Klevit
Professor of Biochemistry; Adj. Prof. of Pharmacology; Adj. Prof. of Chemistry
Affiliations
UW Graduate Programs: Biochemistry, Pharmacology, BPSD, MCB
UW/FHCRC Cancer Consortium
Select Publications
Dove KK, Olszewski JL, Martino L, Duda DM, Wu XS, Miller DJ, Reiter KH, Rittinger K, Schulman BA, Klevit RE. Structural Studies of HHARI/UbcH7~Ub reveal a unique mechanism of E2~Ub conformational restriction by RBR RING1. STRUCTURE, 2017 Jun 6;25(6):890-900.e5. doi: 10.1016/j.str.2017.04.013 Epub 2017 May 25. PubMed PMID: 28552575. PubMed Central: PMC5462532.
Stewart MD, Zelin E, Dhall A, Walsh T, Upadhyay E, Corn JE, Chatterjee C, King MC, Klevit RE. BARD1 is necessary for ubiquitylation of nucleosomal histone H2A and for transcriptional regulation of estrogen metabolism genes. Proc Natl Acad Sci U S A. 2018 Jan 24. pii: 201715467. doi: 10.1073/pnas.1715467115. [Epub ahead of print] PubMed PMID: 29367421.
Baughman HER, Clouser AF, Klevit RE, Nath A. HspB1 and Hsc70 chaperones engage distinct tau species and have different inhibitory effects on amyloid formation. J Biol Chem. 2018 Feb 23;293(8):2687-2700. doi: 10.1074/jbc.M117.803411. PubMed PMID: 29298892.
Tuttle LM, Pacheco D, Warfield L, Luo J, Ranish J, Hahn S, Klevit RE. Gcn4-Mediator Specificity Is Mediated by a Large and Dynamic Fuzzy Protein-Protein Complex. Cell Rep. 2018 Mar 20;22(12):3251-3264. doi: 10.1016/j.celrep.2018.02.097. PubMed PMID: 29562181.
DaRosa PA, Harrison JS, Zelter A, Davis TN, Brzovic P, Kuhlman B, Klevit RE. A Bifunctional Role for the UHRF1 UBL Domain in the Control of Hemi-methylated DNA-Dependent Histone Ubiquitylation. Mol Cell. 2018 Nov 15;72(4):753-765.e6. doi: 10.1016/j.molcel.2018.09.029. Epub 2018 Nov 1. PubMed PMID: 30392931; PubMed Central PMCID: PMC6239910.
Rachel Klevit
Professor of Biochemistry; Adj. Prof. of Pharmacology; Adj. Prof. of Chemistry
Affiliations
UW Graduate Programs: Biochemistry, Pharmacology, BPSD, MCB
UW/FHCRC Cancer Consortium