Kirandeep K. Deol

University of California, Berkeley

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Trends

Author Order

Document Type

Co-Authors

Eric R. Strieter

University of Massachusetts Amherst

Gilles Muller

San Jose State University

James A. Olzmann

University of California, Berkeley

J. A. Gareth Williams

Durham University

Jochen Autschbach

University at Buffalo, State University of New York

Jeanne Crassous

Université de Rennes

Monika Srebro‐Hooper

Jagiellonian University

Nicolas Vanthuyne

Centre National de la Recherche Scientifique

Christian Roussel

Aix-Marseille Université

Régis Réau

Institut des Sciences Chimiques de Rennes

Cooperative Institutions

University of California, Berkeley

Stanford University

Centre National de la Recherche Scientifique

University of California, San Francisco

University of Massachusetts Amherst

Université de Rennes

Institut des Sciences Chimiques de Rennes

Institut de Physique de Rennes

Harvard University

University of Wisconsin–Madison

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

A Cryptic K48 Ubiquitin Chain Binding Site on UCH37 is Required for its Role in Proteasomal Degradation

bioRxiv (Cold Spring Harbor Laboratory) (2021)

Jiale Du Sándor Babik Yanfeng Li Kirandeep K. Deol Stephen J. Eyles

SUMMARY Degradation by the 26S proteasome is an intricately regulated process fine-tuned by the precise nature of ubiquitin modifications attached to a protein substrate. By debranching ubiquitin chains composed of K48 linkages, the proteasome-associated ubiquitin C-terminal hydrolase UCHL5/UCH37 serves as a positive regulator of protein degradation. How UCH37 achieves specificity for K48 chains is unclear. Here, we use a combination of hydrogen-deuterium mass spectrometry, chemical crosslinking, small-angle X-ray scattering, NMR, molecular docking, and targeted mutagenesis to uncover a cryptic K48 ubiquitin chain specific binding site on the opposite face of UCH37 relative to the canonical S1 ubiquitin-binding site. Biochemical assays demonstrate the K48 chain-specific binding site is required for chain debranching and proteasome-mediated degradation of proteins modified with branched chains. Using quantitative proteomics, translation shutoff experiments, and linkage-specific affinity tools, we then identify specific proteins whose degradation depends on the debranching activity of UCH37. Our findings suggest that UCH37 and potentially other DUBs could use more than one S1 site to perform different biochemical functions.

10.1101/2021.11.15.468727

Cite

Citations (1)

Ubiquitin Chain Enrichment Middle-Down Mass Spectrometry Enables Characterization of Branched Ubiquitin Chains in Cellulo

Analytical Chemistry (2017)

Sean O. Crowe Ambar S. J. B. Rana Kirandeep K. Deol Ying Ge Eric R. Strieter

Ubiquitin (Ub) has a broad functional range that has been ascribed to the formation of an array of polymeric ubiquitin chains. Understanding the precise roles of ubiquitin chains, however, is difficult due to their complex chain topologies. Branched ubiquitin chains are particularly challenging, as multiple modifications on a single ubiquitin preclude the use of standard bottom-up proteomic approaches. Developing methods to overcome these challenges is crucial considering evidence suggesting branched chains regulate the stability of proteins. In this study, we employ Ubiquitin Chain Enrichment Middle-down Mass Spectrometry (UbiChEM-MS) to identify branched chains that cannot be detected using bottom-up proteomic methods. Specifically, we employ tandem ubiquitin binding entities (TUBEs) and the K29-selective Npl4 Zinc Finger 1 (NZF1) domain from the deubiquitinase TRABID to enrich for chains from human cells. Minimal trypsinolysis followed by high resolution mass spectrometric analysis reveals that Ub chain branching can indeed be detected using both Ub binding domains (UBDs) tested at endogenous levels. We find that ∼1% of chains isolated with TUBEs contain Ub branch points, with this value rising to ∼4% after proteasome inhibition. Electron-transfer dissociation (ETD) analysis indicates the presence of K48 in these branched chains. The use of the NZF1 domain reveals that ∼4% of the isolated chains contain branch points with no apparent dependence on proteasome inhibition. Our results demonstrate an effective strategy for detecting and characterizing the dynamics of branched conjugates under different cellular conditions.

Deubiquitinating enzyme

10.1021/acs.analchem.6b03675

Cite

Citations (49)

Correction to Ubiquitin Chain Enrichment Middle-Down Mass Spectrometry Enables Characterization of Branched Ubiquitin Chains in Cellulo

Analytical Chemistry (2017)

Sean O. Crowe Ambar S. J. B. Rana Kirandeep K. Deol Ying Ge Eric R. Strieter

ADVERTISEMENT RETURN TO ISSUEPREVAddition/CorrectionNEXTORIGINAL ARTICLEThis notice is a correctionCorrection to Ubiquitin Chain Enrichment Middle-Down Mass Spectrometry Enables Characterization of Branched Ubiquitin Chains in CelluloSean O. Crowe, Ambar S. J. B. Rana, Kirandeep K. Deol, Ying Ge, and Eric R. Strieter*Cite this: Anal. Chem. 2017, 89, 17, 9610Publication Date (Web):August 9, 2017Publication History Published online9 August 2017Published inissue 5 September 2017https://pubs.acs.org/doi/10.1021/acs.analchem.7b02855https://doi.org/10.1021/acs.analchem.7b02855correctionACS PublicationsCopyright © 2017 American Chemical Society. This publication is available under these Terms of Use. Request reuse permissions This publication is free to access through this site. Learn MoreArticle Views673Altmetric-Citations1LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail PDF (561 KB) Get e-Alertsclose Get e-Alerts

Characterization

Chain (unit)

10.1021/acs.analchem.7b02855

Cite

Citations (1)

CCDC 846305: Experimental Crystal Structure Determination

The Cambridge Structural Database (2014)

Chengshuo Shen Emmanuel Anger Monika Srebro‐Hooper Nicolas Vanthuyne Kirandeep K. Deol

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

10.5517/ccxdn53

Cite

Citations (0)

The ubiquitin proteoform problem

Current Opinion in Chemical Biology (2021)

Kirandeep K. Deol Eric R. Strieter

Posttranslational modification

10.1016/j.cbpa.2021.02.015

Cite

Citations (16)

CCDC 827045: Experimental Crystal Structure Determination

The Cambridge Structural Database (2014)

Chengshuo Shen Emmanuel Anger Monika Srebro‐Hooper Nicolas Vanthuyne Kirandeep K. Deol

10.5517/ccwrlw2

Cite

Citations (0)

A cryptic K48 ubiquitin chain binding site on UCH37 is required for its role in proteasomal degradation

eLife (2022)

Jiale Du Sándor Babik Yanfeng Li Kirandeep K. Deol Stephen J. Eyles

Degradation by the 26 S proteasome is an intricately regulated process fine tuned by the precise nature of ubiquitin modifications attached to a protein substrate. By debranching ubiquitin chains composed of K48 linkages, the proteasome-associated ubiquitin C-terminal hydrolase UCHL5/UCH37 serves as a positive regulator of protein degradation. How UCH37 achieves specificity for K48 chains is unclear. Here, we use a combination of hydrogen-deuterium mass spectrometry, chemical crosslinking, small-angle X-ray scattering, nuclear magnetic resonance (NMR), molecular docking, and targeted mutagenesis to uncover a cryptic K48 ubiquitin (Ub) chain-specific binding site on the opposite face of UCH37 relative to the canonical S1 (cS1) ubiquitin-binding site. Biochemical assays demonstrate the K48 chain-specific binding site is required for chain debranching and proteasome-mediated degradation of proteins modified with branched chains. Using quantitative proteomics, translation shutoff experiments, and linkage-specific affinity tools, we then identify specific proteins whose degradation depends on the debranching activity of UCH37. Our findings suggest that UCH37 and potentially other DUBs could use more than one S1 site to perform different biochemical functions.

Protein Degradation

10.7554/elife.76100

Cite

Citations (18)

A Cryptic K48 Ubiquitin Chain Binding Site on UCH37 is Required for its Role in Proteasomal Degradation

bioRxiv (Cold Spring Harbor Laboratory) (2021)

Jiale Du Sándor Babik Yanfeng Li Kirandeep K. Deol Stephen J. Eyles

Degradation by the 26S proteasome is an intricately regulated process fine-tuned by the precise nature of ubiquitin modifications attached to a protein substrate. By debranching ubiquitin chains composed of K48 linkages, the proteasome-associated ubiquitin C-terminal hydrolase UCHL5/UCH37 serves as a positive regulator of protein degradation. How UCH37 achieves specificity for K48 chains is unclear. Here, we use a combination of hydrogen-deuterium mass spectrometry, chemical crosslinking, small-angle X-ray scattering, NMR, molecular docking, and targeted mutagenesis to uncover a cryptic K48 ubiquitin chain specific binding site on the opposite face of UCH37 relative to the canonical S1 ubiquitin-binding site. Biochemical assays demonstrate the K48 chain-specific binding site is required for chain debranching and proteasome-mediated degradation of proteins modified with branched chains. Using quantitative proteomics, translation shutoff experiments, and linkage-specific affinity tools, we then identify specific proteins whose degradation depends on the debranching activity of UCH37. Our findings suggest that UCH37 and potentially other DUBs could use more than one S1 site to perform different biochemical functions.

10.17632/423f5cj79n.1

Cite

Citations (0)

CCDC 934302: Experimental Crystal Structure Determination

The Cambridge Structural Database (2015)

Nidal Saleh Barry Moore Monika Srebro‐Hooper Nicolas Vanthuyne Loı̈c Toupet

10.5517/cc10c6sc

Cite

Citations (0)

Ribosome stalling during selenoprotein translation exposes a ferroptosis vulnerability

Nature Chemical Biology (2022)

Zhipeng Li Lucas Ferguson Kirandeep K. Deol Melissa A. Roberts Leslie Magtanong