6c16: Difference between revisions
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The | ==Ubiquitin variant (UbV.Fbl10.1) bound to a human Skp1-Fbl11 fragment complex.== | ||
<StructureSection load='6c16' size='340' side='right'caption='[[6c16]], [[Resolution|resolution]] 3.27Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6c16]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6C16 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6C16 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.27Å</td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6c16 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6c16 OCA], [https://pdbe.org/6c16 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6c16 RCSB], [https://www.ebi.ac.uk/pdbsum/6c16 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6c16 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/SKP1_HUMAN SKP1_HUMAN] Essential component of the SCF (SKP1-CUL1-F-box protein) ubiquitin ligase complex, which mediates the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription. In the SCF complex, serves as an adapter that links the F-box protein to CUL1. SCF(BTRC) mediates the ubiquitination of NFKBIA at 'Lys-21' and 'Lys-22'; the degradation frees the associated NFKB1-RELA dimer to translocate into the nucleus and to activate transcription. SCF(Cyclin F) directs ubiquitination of CP110.<ref>PMID:16209941</ref> <ref>PMID:20181953</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Skp1-Cul1-F-box (SCF) E3 ligases constitute the largest and best-characterized family of the multisubunit E3 ligases with important cellular functions and numerous disease links. The specificity of an SCF E3 ligase is established by one of the 69 human F-box proteins that are recruited to Cul1 through the Skp1 adaptor. We previously reported generation of ubiquitin variants (UbVs) targeting Fbw7 and Fbw11, which inhibit ligase activity by binding at the F-box-Skp1 interface to competitively displace Cul1. In the present study, we employed an optimized engineering strategy to generate specific binding UbVs against 17 additional Skp1-F-box complexes. We validated our design strategy and uncovered the structural basis of binding specificity by crystallographic analyses of representative UbVs bound to Skp1-Fbl10 and Skp1-Fbl11. Our study highlights the power of combining phage display with structure-based design to develop UbVs targeting specific protein surfaces. | |||
A Structure-Based Strategy for Engineering Selective Ubiquitin Variant Inhibitors of Skp1-Cul1-F-Box Ubiquitin Ligases.,Gorelik M, Manczyk N, Pavlenco A, Kurinov I, Sidhu SS, Sicheri F Structure. 2018 Jun 26. pii: S0969-2126(18)30210-7. doi:, 10.1016/j.str.2018.06.004. PMID:30033217<ref>PMID:30033217</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 6c16" style="background-color:#fffaf0;"></div> | ||
[[Category: Manczyk | |||
==See Also== | |||
*[[Lysine-specific histone demethylase 3D structures|Lysine-specific histone demethylase 3D structures]] | |||
*[[3D structures of ubiquitin|3D structures of ubiquitin]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Manczyk N]] | |||
[[Category: Sicheri F]] | |||