3L82

X-ray Crystal structure of TRF1 and Fbx4 complex

Summary for 3L82

• Entry DOI: 10.2210/pdb3l82/pdb
• Descriptor: Telomeric repeat-binding factor 1, F-box only protein 4 (3 entities in total)
• Functional Keywords: trfh domain, helix, gtpase domain, adp-ribosylation, cell cycle, cell division, chromosomal protein, cytoskeleton, dna-binding, mitosis, nucleus, phosphoprotein, telomere, ubl conjugation pathway
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: P54274; Cytoplasm (By similarity): Q9UKT5
• Total number of polymer chains: 2
• Total formula weight: 50924.59

Authors

Zeng, Z.X.,Wang, W.,Yang, Y.T.,Chen, Y.,Yang, X.M.,Diehl, J.A.,Liu, X.D.,Lei, M. (deposition date: 2009-12-29, release date: 2010-03-09, Last modification date: 2024-10-30)

Primary citation

Zeng, Z.,Wang, W.,Yang, Y.,Chen, Y.,Yang, X.,Diehl, J.A.,Liu, X.,Lei, M.
Structural Basis of Selective Ubiquitination of TRF1 by SCF(Fbx4)
Dev.Cell, 18:214-225, 2010

PubMed Abstract: 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 A 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 SCF(Fbx4) is regulated by another telomere protein, TIN2. Our results reveal an atypical small GTPase domain within Fbx4 as a substrate-binding motif for SCF(Fbx4) and uncover a mechanism for selective ubiquitination and degradation of TRF1 in telomere homeostasis control.

PubMed: 20159592
DOI: 10.1016/j.devcel.2010.01.007

Experimental method

X-RAY DIFFRACTION (2.4 Å)