标题:Structural Basis of Selective Ubiquitination of TRF1 by SCFFbx4
作者:Zeng, Zhixiong; Wang, Wei; Yang, Yuting; Chen, Yong; Yang, Xiaomei; Diehl, J. Alan; Liu, Xuedong; Lei, Ming
作者机构:[Wang, Wei; Yang, Xiaomei; Liu, Xuedong] Univ Colorado, Dept Chem & Biochem, Boulder, CO 80309 USA.; [Zeng, Zhixiong; Yang, Yuting; Chen, Yong; Lei, 更多
通讯作者:Liu, XD
通讯作者地址:[Liu, XD]Univ Colorado, Dept Chem & Biochem, Boulder, CO 80309 USA.
来源:DEVELOPMENTAL CELL
出版年:2010
卷:18
期:2
页码:214-225
DOI:10.1016/j.devcel.2010.01.007
摘要:TRF1 is a critical regulator of telomere length. As such, TRF1 levels are regulated by ubiquitin-dependent proteolysis via an SCF E3 ligase where Fbx4 contributes to substrate specification. Here, we report the crystal structure of the Fbx4-TRF1 complex at 2.4 angstrom resolution. Fbx4 contains an unusual substrate-binding domain that adopts a small GTPase fold. Strikingly, this atypical GTPase domain of Fbx4 binds to a globular domain of TRF1 through an intermolecular beta sheet, instead of recognizing short peptides/degrons as often seen in other F-box protein-substrate complexes. Importantly, mutations in this interface abrogate Fbx4-dependent TRF1 binding and ubiquitination. Furthermore, the data demonstrate that recognition of TRF1 by SCFFbx4 is regulated by another telomere protein, TIN2. Our results reveal an atypical small GTPase domain within Fbx4 as a substrate-binding motif for SCFFbx4 and uncover a mechanism for selective ubiquitination and degradation of TRF1 in telomere homeostasis control.
收录类别:SCOPUS;SCIE
WOS核心被引频次:37
Scopus被引频次:41
资源类型:期刊论文
原文链接:https://www.scopus.com/inward/record.uri?eid=2-s2.0-76249092490&doi=10.1016%2fj.devcel.2010.01.007&partnerID=40&md5=0069e7c27b577670a1f028cd83d1acec
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