There are no files associated with this item.
Full metadata record
DC Field | Value | Language |
---|---|---|
dc.citation.endPage | 2148 | - |
dc.citation.number | 12 | - |
dc.citation.startPage | 2136 | - |
dc.citation.title | BIOCHEMISTRY | - |
dc.citation.volume | 54 | - |
dc.contributor.author | Trung Thanh Thach | - |
dc.contributor.author | Lee, Namsoo | - |
dc.contributor.author | Shin, Donghyuk | - |
dc.contributor.author | Han, Seungsu | - |
dc.contributor.author | Kim, Gyuhee | - |
dc.contributor.author | Kim, Hongtae | - |
dc.contributor.author | Lee, Sangho | - |
dc.date.accessioned | 2023-12-22T01:36:51Z | - |
dc.date.available | 2023-12-22T01:36:51Z | - |
dc.date.created | 2018-09-19 | - |
dc.date.issued | 2015-03 | - |
dc.description.abstract | Rad18 is a key factor in double-strand break DNA damage response (DDR) pathways via its association with K63-linked polyubiquitylated chromatin proteins through its bipartite ubiquitin-binding domains UBZ and LRM with extra residues between them. Rad18 binds K63-linked polyubiquitin chains as well as K48-linked ones and monoubiquitin. However, the detailed molecular basis of polyubiquitin recognition by UBZ and LRM remains unclear. Here, we examined the interaction of Rad18(201-240), including UBZ and LRM, with linear polyubiquitin chains that are structurally similar to the K63-linked ones. Rad18(201-240) binds linear polyubiquitin chains (Ub(2)Ub(4)) with affinity similar to that of a K63-linked one for diubiquitin. Ab initio modeling suggests that LRM and the extra residues at the C-terminus of UBZ (residues 227-237) likely form a continuous helix, termed the extended LR motif (ELRM). We obtained a molecular envelope for Rad18 UBZ-ELRM:linear Ub2 by small-angle X-ray scattering and derived a structural model for the complex. The Rad18:linear Ub(2) model indicates that ELRM enhances the binding of Rad18 with linear polyubiquitin by contacting the proximal ubiquitin moiety. Consistent with the structural analysis, mutational studies showed that residues in ELRM affect binding with linear Ub(2), not monoubiquitin. In cell data support the idea that ELRM is crucial in the localization of Rad18 to DNA damage sites. Specifically, E227 seems to be the most critical in polyubiquitin binding and localization to nuclear foci. Finally, we reveal that the ubiquitin-binding domains of Rad18 bind linear Ub(2) more tightly than those of RAP80, providing a quantitative basis for blockage of RAP80 at DSB sites. Taken together, our data demonstrate that Rad18(201-240) forms continuous ubiquitin-binding domains, comprising UBZ and ELRM, and provides a structural framework for polyubiquitin recognition by Rad18 in the DDR pathway at a molecular level. | - |
dc.identifier.bibliographicCitation | BIOCHEMISTRY, v.54, no.12, pp.2136 - 2148 | - |
dc.identifier.doi | 10.1021/bi5012546 | - |
dc.identifier.issn | 0006-2960 | - |
dc.identifier.scopusid | 2-s2.0-84964240666 | - |
dc.identifier.uri | https://scholarworks.unist.ac.kr/handle/201301/24889 | - |
dc.identifier.url | https://pubs.acs.org/doi/10.1021/bi5012546 | - |
dc.identifier.wosid | 000352245600005 | - |
dc.language | 영어 | - |
dc.publisher | AMER CHEMICAL SOC | - |
dc.title | Molecular Determinants of Polyubiquitin Recognition by Continuous Ubiquitin-Binding Domains of Rad18 | - |
dc.type | Article | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.subject.keywordPlus | DNA-DAMAGE RESPONSE | - |
dc.subject.keywordPlus | X-RAY-SCATTERING | - |
dc.subject.keywordPlus | ZINC-FINGER | - |
dc.subject.keywordPlus | PCNA MONOUBIQUITINATION | - |
dc.subject.keywordPlus | STRUCTURE PREDICTION | - |
dc.subject.keywordPlus | CRYSTAL-STRUCTURE | - |
dc.subject.keywordPlus | STRUCTURAL BASIS | - |
dc.subject.keywordPlus | RAP80 | - |
dc.subject.keywordPlus | PROTEINS | - |
dc.subject.keywordPlus | REPAIR | - |
Items in Repository are protected by copyright, with all rights reserved, unless otherwise indicated.
Tel : 052-217-1404 / Email : scholarworks@unist.ac.kr
Copyright (c) 2023 by UNIST LIBRARY. All rights reserved.
ScholarWorks@UNIST was established as an OAK Project for the National Library of Korea.