7y4q

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'''Unreleased structure'''
 
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The entry 7y4q is ON HOLD until Paper Publication
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==Semaphorin 6D in complex with Plexin A1==
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<StructureSection load='7y4q' size='340' side='right'caption='[[7y4q]], [[Resolution|resolution]] 4.70&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[7y4q]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7Y4Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Y4Q FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7y4q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7y4q OCA], [https://pdbe.org/7y4q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7y4q RCSB], [https://www.ebi.ac.uk/pdbsum/7y4q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7y4q ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/PLXA1_HUMAN PLXA1_HUMAN] Coreceptor for SEMA3A, SEMA3C, SEMA3F and SEMA6D. Necessary for signaling by class 3 semaphorins and subsequent remodeling of the cytoskeleton. Plays a role in axon guidance, invasive growth and cell migration. Class 3 semaphorins bind to a complex composed of a neuropilin and a plexin. The plexin modulates the affinity of the complex for specific semaphorins, and its cytoplasmic domain is required for the activation of down-stream signaling events in the cytoplasm (By similarity).
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Semaphorins constitute a large family of secreted and membrane-bound proteins that signal through cell-surface receptors, plexins. Semaphorins generally use low-affinity protein-protein interactions to bind with their specific plexin(s) and regulate distinct cellular processes such as neurogenesis, immune response, and organogenesis. Sema6D is a membrane-bound semaphorin that interacts with class A plexins. Sema6D exhibited differential binding affinities to class A plexins in prior cell-based assays, but the molecular mechanism underlying this selectivity is not well understood. Therefore, we performed hybrid in vitro/in silico analysis to examine the binding mode of Sema6D to class A plexins and to identify residues that give rise to the differential affinities and thus contribute to the selectivity within the same class of semaphorins. Our biophysical binding analysis indeed confirmed that Sema6D has a higher affinity for Plexin-A1 than for other class A plexins, consistent with the binding selectivity observed in the previous cell-based assays. Unexpectedly, our present crystallographic analysis of the Sema6D-Plexin-A1 complex showed that the pattern of polar interactions is not interaction-specific because it matches the pattern in the prior structure of the Sema6A-Plexin-A2 complex. Thus, we performed in silico alanine scanning analysis and discovered hotspot residues that selectively stabilized the Sema6D-Plexin-A1 pair via van der Waals interactions. We then validated the contribution of these hotspot residues to the variation in binding affinity with biophysical binding analysis and molecular dynamics simulations on the mutants. Ultimately, our present results suggest that shape complementarity in the binding interfaces is a determinant for binding selectivity.
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Authors:
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Hybrid in vitro/in silico analysis of low-affinity protein-protein interactions that regulate signal transduction by Sema6D.,Tanaka T, Ekimoto T, Nagatomo M, Neyazaki M, Shimoji E, Yamane T, Kanagawa S, Oi R, Mihara E, Takagi J, Akashi S, Ikeguchi M, Nogi T Protein Sci. 2022 Sep 26:e4452. doi: 10.1002/pro.4452. PMID:36156831<ref>PMID:36156831</ref>
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Description:
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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<div class="pdbe-citations 7y4q" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Rattus norvegicus]]
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[[Category: Neyazaki M]]
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[[Category: Nogi T]]
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[[Category: Tanaka T]]

Revision as of 19:24, 19 October 2022

Semaphorin 6D in complex with Plexin A1

PDB ID 7y4q

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