Structural highlights
Function
TERF1_HUMAN Binds the telomeric double-stranded TTAGGG repeat and negatively regulates telomere length. Involved in the regulation of the mitotic spindle. Component of the shelterin complex (telosome) that is involved in the regulation of telomere length and protection. Shelterin associates with arrays of double-stranded TTAGGG repeats added by telomerase and protects chromosome ends; without its protective activity, telomeres are no longer hidden from the DNA damage surveillance and chromosome ends are inappropriately processed by DNA repair pathways.[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
Structural basis of selective ubiquitination of TRF1 by SCFFbx4.,Zeng Z, Wang W, Yang Y, Chen Y, Yang X, Diehl JA, Liu X, Lei M Dev Cell. 2010 Feb 16;18(2):214-25. PMID:20159592[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ de Lange T. Shelterin: the protein complex that shapes and safeguards human telomeres. Genes Dev. 2005 Sep 15;19(18):2100-10. PMID:16166375 doi:10.1101/gad.1346005
- ↑ Zeng Z, Wang W, Yang Y, Chen Y, Yang X, Diehl JA, Liu X, Lei M. Structural basis of selective ubiquitination of TRF1 by SCFFbx4. Dev Cell. 2010 Feb 16;18(2):214-25. PMID:20159592 doi:10.1016/j.devcel.2010.01.007
