Journal article
STRUCTURALLY DISTINCT UBIQUITIN- AND SUMO-MODIFIED PCNA: IMPLICATIONS FOR THEIR DISTINCT ROLES IN THE DNA DAMAGE RESPONSE
Structure (London), Vol.23(4), pp.724-733
04/07/2015
DOI: 10.1016/j.str.2015.02.008
PMCID: PMC4394044
PMID: 25773143
Abstract
Proliferating cell nuclear antigen (PCNA) is a pivotal replication protein, which also controls cellular responses to DNA damage. Posttranslational modification of PCNA by SUMO and ubiquitin modulate these responses. How the modifiers alter PCNA-dependent DNA repair and damage tolerance pathways is largely unknown. We used hybrid methods to identify atomic models of PCNA
K107
-Ub and PCNA
K164
-SUMO consistent with small angle X-ray scattering (SAXS) data of these complexes in solution. We show that SUMO and ubiquitin have distinct modes of association to PCNA. Ubiquitin adopts discrete docked binding positions. By contrast, SUMO associates by simple tethering and adopts extended flexible conformations. These structural differences are the result of the opposite electrostatic potentials of SUMO and Ub. The unexpected contrast in conformational behavior of Ub-PCNA and SUMO-PCNA has implications for interactions with partner proteins, interacting surfaces accessibility, and access points for pathway regulation.
Details
- Title: Subtitle
- STRUCTURALLY DISTINCT UBIQUITIN- AND SUMO-MODIFIED PCNA: IMPLICATIONS FOR THEIR DISTINCT ROLES IN THE DNA DAMAGE RESPONSE
- Creators
- Susan E Tsutakawa - Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA, 94720 USAChunli Yan - Department of Chemistry, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia 30302 USAXiaojun Xu - Department of Chemistry, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia 30302 USAChristopher P Weinacht - Department of Chemistry and Biochemistry, University of Delaware, Newark, DE 19716 USABret D Freudenthal - Department of Biochemistry, University of Iowa College of Medicine, Iowa City, IA 52242 USAKun Yang - Department of Chemistry and Biochemistry, University of Delaware, Newark, DE 19716 USAZhihao Zhuang - Department of Chemistry and Biochemistry, University of Delaware, Newark, DE 19716 USAM. Todd Washington - Department of Biochemistry, University of Iowa College of Medicine, Iowa City, IA 52242 USAJohn A Tainer - Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA, 94720 USAIvaylo Ivanov - Department of Chemistry, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia 30302 USA
- Resource Type
- Journal article
- Publication Details
- Structure (London), Vol.23(4), pp.724-733
- DOI
- 10.1016/j.str.2015.02.008
- PMID
- 25773143
- PMCID
- PMC4394044
- NLM abbreviation
- Structure
- ISSN
- 0969-2126
- eISSN
- 1878-4186
- Grant note
- DOI: 10.13039/100000001, name: NSF CAREER, award: MCB-1149521; DOI: 10.13039/100008545, name: Georgia State University start-up funds; DOI: 10.13039/100000054, name: NCI, award: P01 CA092584; DOI: 10.13039/100000054, name: NCI, award: R01 CA081967; DOI: 10.13039/100000001, name: NSF, award: MCB-0953764, R01 GM108027; DOI: 10.13039/100006132, name: U.S. Department of Energy Office of Science, award: DE-AC02-05CH11231; DOI: 10.13039/100006206, name: Integrated Diffraction Analysis Technologies (IDAT) program, award: DE-AC02-05CH11231; DOI: 10.13039/100000002, name: NIH MINOS, award: R01GM105404
- Language
- English
- Date published
- 04/07/2015
- Academic Unit
- Radiation Oncology; Biochemistry and Molecular Biology
- Record Identifier
- 9984024517602771
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