We have moved all aspects of this umbrella project forward during 2013. We discovered that C-terminal domains within ATPase proteins that dock against the proteasome's core particle undergo dynamic exchange between an expected 4-helix bundle and a partially unfolded state. We provided evidence that this exchange is important for interactions with chaperones involved in proteasome assembly. In unpublished work, we have moved forward the resolution of the 3D structures for multiple protein complexes, including a new ubiquitin binding motif.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC011490-01
Application #
8763562
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2013
Total Cost
$702,614
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Randles, Leah; Anchoori, Ravi K; Roden, Richard B S et al. (2016) The Proteasome Ubiquitin Receptor hRpn13 and Its Interacting Deubiquitinating Enzyme Uch37 Are Required for Proper Cell Cycle Progression. J Biol Chem 291:8773-83
Finley, Daniel; Chen, Xiang; Walters, Kylie J (2016) Gates, Channels, and Switches: Elements of the Proteasome Machine. Trends Biochem Sci 41:77-93
Chen, Xiang; Walters, Kylie J (2016) (1)H, (15)N, (13)C resonance assignments for Saccharomyces cerevisiae Rad23 UBL domain. Biomol NMR Assign 10:291-5
Shi, Yuan; Chen, Xiang; Elsasser, Suzanne et al. (2016) Rpn1 provides adjacent receptor sites for substrate binding and deubiquitination by the proteasome. Science 351:
Yu, Clinton; Yang, Yingying; Wang, Xiaorong et al. (2016) Characterization of Dynamic UbR-Proteasome Subcomplexes by In vivo Cross-linking (X) Assisted Bimolecular Tandem Affinity Purification (XBAP) and Label-free Quantitation. Mol Cell Proteomics 15:2279-92
Nowicka, Urszula; Hoffman, Morgan; Randles, Leah et al. (2016) Mycobacterium tuberculosis copper-regulated protein SocB is an intrinsically disordered protein that folds upon interaction with a synthetic phospholipid bilayer. Proteins 84:193-200
Lu, Xiuxiu; Liu, Fen; Durham, Sarah E et al. (2015) A High Affinity hRpn2-Derived Peptide That Displaces Human Rpn13 from Proteasome in 293T Cells. PLoS One 10:e0140518
Chen, Xiang; Walters, Kylie J (2015) Structural plasticity allows UCH37 to be primed by RPN13 or locked down by INO80G. Mol Cell 57:767-8
Anchoori, Ravi K; Karanam, Balasubramanyam; Peng, Shiwen et al. (2013) A bis-benzylidine piperidone targeting proteasome ubiquitin receptor RPN13/ADRM1 as a therapy for cancer. Cancer Cell 24:791-805
Ehlinger, Aaron; Walters, Kylie J (2013) Structural insights into proteasome activation by the 19S regulatory particle. Biochemistry 52:3618-28

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