3l82

From Proteopedia

(Difference between revisions)

Revision as of 00:08, 25 December 2014

X-ray Crystal structure of TRF1 and Fbx4 complex

Structural highlights

3l82 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
NonStd Res:
Gene:	TERF1, PIN2, TRBF1, TRF, TRF1 (Homo sapiens), FBXO4, FBX4 (Homo sapiens)
Resources:	FirstGlance, OCA, RCSB, PDBsum

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] [FBX4_HUMAN] Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex that mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Promotes ubiquitination of CCND1 and its subsequent proteasomal degradation. Recognizes TERF1 and promotes its ubiquitination together with UBE2D1.^[2] ^[3] ^[4] ^[5] ^[6]

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^[7]

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
↑ Cenciarelli C, Chiaur DS, Guardavaccaro D, Parks W, Vidal M, Pagano M. Identification of a family of human F-box proteins. Curr Biol. 1999 Oct 21;9(20):1177-9. PMID:10531035 doi:S0960-9822(00)80020-2
↑ Lee TH, Perrem K, Harper JW, Lu KP, Zhou XZ. The F-box protein FBX4 targets PIN2/TRF1 for ubiquitin-mediated degradation and regulates telomere maintenance. J Biol Chem. 2006 Jan 13;281(2):759-68. Epub 2005 Nov 7. PMID:16275645 doi:10.1074/jbc.M509855200
↑ Barbash O, Zamfirova P, Lin DI, Chen X, Yang K, Nakagawa H, Lu F, Rustgi AK, Diehl JA. Mutations in Fbx4 inhibit dimerization of the SCF(Fbx4) ligase and contribute to cyclin D1 overexpression in human cancer. Cancer Cell. 2008 Jul 8;14(1):68-78. doi: 10.1016/j.ccr.2008.05.017. PMID:18598945 doi:10.1016/j.ccr.2008.05.017
↑ 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
↑ Li Y, Hao B. Structural basis of dimerization-dependent ubiquitination by the SCF(Fbx4) ubiquitin ligase. J Biol Chem. 2010 Apr 30;285(18):13896-906. Epub 2010 Feb 24. PMID:20181953 doi:10.1074/jbc.M110.111518
↑ 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

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3l82"

@@ Line 7: / Line 7: @@
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3l82 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3l82 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3l82 RCSB], [http://www.ebi.ac.uk/pdbsum/3l82 PDBsum]</span></td></tr>
 </table>
+== Function ==
+[[http://www.uniprot.org/uniprot/TERF1_HUMAN 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.<ref>PMID:16166375</ref>  [[http://www.uniprot.org/uniprot/FBX4_HUMAN FBX4_HUMAN]] Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex that mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Promotes ubiquitination of CCND1 and its subsequent proteasomal degradation. Recognizes TERF1 and promotes its ubiquitination together with UBE2D1.<ref>PMID:10531035</ref> <ref>PMID:16275645</ref> <ref>PMID:18598945</ref> <ref>PMID:20159592</ref> <ref>PMID:20181953</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]

3l82

From Proteopedia

Revision as of 00:08, 25 December 2014

X-ray Crystal structure of TRF1 and Fbx4 complex

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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