View source for 5sxp


==STRUCTURAL BASIS FOR THE INTERACTION BETWEEN ITCH PRR AND BETA-PIX==
<StructureSection load='5sxp' size='340' side='right'caption='[[5sxp]], [[Resolution|resolution]] 1.65&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5sxp]] 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=5SXP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5SXP 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]] 1.65&#8491;</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=5sxp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5sxp OCA], [https://pdbe.org/5sxp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5sxp RCSB], [https://www.ebi.ac.uk/pdbsum/5sxp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5sxp ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ARHG7_HUMAN ARHG7_HUMAN] Acts as a RAC1 guanine nucleotide exchange factor (GEF) and can induce membrane ruffling. Functions in cell migration, attachment and cell spreading. Promotes targeting of RAC1 to focal adhesions (By similarity). May function as a positive regulator of apoptosis. Downstream of NMDA receptors and CaMKK-CaMK1 signaling cascade, promotes the formation of spines and synapses in hippocampal neurons.<ref>PMID:19041750</ref> <ref>PMID:18716323</ref> <ref>PMID:18184567</ref> 
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== Publication Abstract from PubMed ==
The ligase Itch plays major roles in signalling pathways by inducing ubiquitylation-dependent degradation of several substrates. Substrate recognition and binding is critical for the regulation of this reaction. Like closely related ligases, Itch can interact with proteins containing a PPxY motif via its WW domains. In addition to these WW domains, Itch possesses a proline-rich region (PRR) that has been shown to interact with several Src Homology 3 (SH3) domain-containing proteins. We have previously established that despite the apparent surface uniformity and conserved fold of SH3 domains, they display different binding mechanisms and affinities for their interaction with the PRR of Itch. Here, we attempt to determine the molecular bases underlying the wide range of binding properties of the Itch PRR. Using pull-down assays combined with mass spectrometry analysis, we show that the Itch PRR preferentially forms complexes with Endophilins, Amphyphisins and Pacsins, but can also target a variety of other SH3 domain-containing proteins. In addition, we map the binding sites of these proteins using a combination of PRR sub-sequences and mutants. We find that different SH3 domains target distinct proline-rich sequences overlapping significantly. We also structurally analyze these protein complexes using crystallography and molecular modelling. These structures depict the position of Itch PRR engaged in a 1:2 protein complex with beta-PIX and a 1:1 complex with the other SH3 domain-containing proteins. Taken together, these results reveal the binding preferences of the Itch PRR towards its most common SH3 domain-containing partners, and demonstrate that the PRR region is sufficient for binding.

Molecular Basis of Interactions Between SH3 Domain-Containing Proteins and the Proline-Rich Region of the Ubiquitin Ligase Itch.,Desrochers G, Cappadocia L, Lussier-Price M, Ton AT, Ayoubi R, Serohijos A, Omichinski JG, Angers A J Biol Chem. 2017 Feb 24. pii: jbc.M116.754440. doi: 10.1074/jbc.M116.754440. PMID:28235806<ref>PMID:28235806</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Angers A]]
[[Category: Cappadocia L]]
[[Category: Desrochers G]]
[[Category: Lussier-Price M]]
[[Category: Omichinski JG]]