8bf4
From Proteopedia
Crystal structure of Mouse Plexin-B1 (20-535) in complex with VHH15 and VHH14
Structural highlights
FunctionPLXB1_MOUSE Receptor for SEMA4D (PubMed:19788569). Plays a role in GABAergic synapse development (PubMed:23699507, PubMed:29981480). Mediates SEMA4A- and SEMA4D-dependent inhibitory synapse development (PubMed:23699507, PubMed:29981480). Plays a role in RHOA activation and subsequent changes of the actin cytoskeleton (By similarity). Plays a role in axon guidance, invasive growth and cell migration (By similarity).[UniProtKB:O43157][1] [2] [3] Publication Abstract from PubMedPlexin-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[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Camelidae | Large Structures | Mus musculus | Carr M | Cowan R | Hall G
