8b3k: Difference between revisions
No edit summary |
No edit summary |
||
Line 1: | Line 1: | ||
==Crystal structure of human Plexin-B1 (20-535) in the unbound state== | |||
<StructureSection load='8b3k' size='340' side='right'caption='[[8b3k]], [[Resolution|resolution]] 2.69Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8b3k]] is a 2 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=8B3K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8B3K FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CD:CADMIUM+ION'>CD</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=8b3k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8b3k OCA], [https://pdbe.org/8b3k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8b3k RCSB], [https://www.ebi.ac.uk/pdbsum/8b3k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8b3k ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/PLXB1_HUMAN PLXB1_HUMAN] Receptor for SEMA4D. Plays a role in RHOA activation and subsequent changes of the actin cytoskeleton. Plays a role in axon guidance, invasive growth and cell migration.<ref>PMID:12198496</ref> <ref>PMID:12196628</ref> <ref>PMID:15210733</ref> <ref>PMID:19843518</ref> <ref>PMID:20877282</ref> <ref>PMID:21912513</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Plexin-B1 is a receptor for the cell surface semaphorin, Sema4D. This signalling system has been implicated in a variety of human diseases, including cancer, multiple sclerosis and osteoporosis. Whilst inhibitors of the Plexin-B1:Sema4D interaction have been previously reported, understanding their mechanism has been hindered by an incomplete structural view of Plexin-B1. In this study, we have raised and characterised a pair of nanobodies that are specific for mouse Plexin-B1, and which inhibit the binding of Sema4D to mouse Plexin-B1 and its biological activity. Structural studies of these nanobodies reveal that they inhibit the binding of Sema4D in an allosteric manner, binding to epitopes not previously reported. In addition, we report the first unbound structure of human Plexin-B1, which reveals that Plexin-B1 undergoes a conformational change on Sema4D binding. These changes mirror those seen upon binding of allosteric peptide modulators, which suggests a new model for understanding Plexin-B1 signalling, and provides a potential innovative route for therapeutic modulation of Plexin-B1. | |||
Nanobody inhibitors of Plexin-B1 identify allostery in plexin-semaphorin interactions and signalling.,Cowan R, Trokter M, Oleksy A, Fedorova M, Sawmynaden K, Worzfeld T, Offermanns S, Matthews D, Carr MD, Hall G J Biol Chem. 2023 Apr 21:104740. doi: 10.1016/j.jbc.2023.104740. PMID:37088134<ref>PMID:37088134</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 8b3k" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Carr M]] | |||
[[Category: Cowan R]] | |||
[[Category: Hall G]] |