8bf4

Crystal structure of Mouse Plexin-B1 (20-535) in complex with VHH15 and VHH14

spinqualitylabelsall models 8bf4, resolution 2.15Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8bf4 is a 6 chain structure with sequence from Camelidae and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.15Å Ligands: CL, EDO, NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PLXB1_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] Publication Abstract from PubMed Plexin-B1 is a receptor for the cell surface semaphorin, Sema4D. This signaling system has been implicated in a variety of human diseases, including cancer, multiple sclerosis and osteoporosis. While 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 characterized 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 signaling and provides a potential innovative route for therapeutic modulation of Plexin-B1. Nanobody inhibitors of Plexin-B1 identify allostery in plexin-semaphorin interactions and signaling.,Cowan R, Trokter M, Oleksy A, Fedorova M, Sawmynaden K, Worzfeld T, Offermanns S, Matthews D, Carr MD, Hall G J Biol Chem. 2023 Jun;299(6):104740. doi: 10.1016/j.jbc.2023.104740. Epub 2023 , Apr 23. PMID:37088134 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Plexin 3D structures

Proteopedia Page Contributors and Editors (what is this?)

OCA