Structural Basis of Selective Ubiquitination of TRF1 by SCF[superscript Fbx4]

Journal Article · Fri Sep 03 04:00:00 EDT 2010 · Dev. Cell

DOI:https://doi.org/10.1016/j.devcel.2010.01.007· OSTI ID:1002646

Zeng, Zhixiong; Wang, Wei; Yang, Yuting; Chen, Yong; Yang, Xiaomei; Diehl, J Alan; Liu, Xuedong; Lei, Ming ^[1]

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1. UPENN

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.

• Research Organization: Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
• Sponsoring Organization: USDOE
• OSTI ID: 1002646
• Journal Information: Dev. Cell, Journal Name: Dev. Cell Journal Issue: (2) ; 02, 2010 Vol. 18
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

36 MATERIALS SCIENCE
CRYSTAL STRUCTURE
HOMEOSTASIS
LIGASES
MUTATIONS
PROTEOLYSIS
RESOLUTION
SUBSTRATES
TELOMERES