8BB7

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

8BB7 の概要

• エントリーDOI: 10.2210/pdb8bb7/pdb
• 分子名称: Plexin-B1, VHH15 Nanobody, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• 機能のキーワード: complex, inhibitor, vhh, nanobody, plexin, semaphorin, allosteric, signaling protein
• 由来する生物種: Mus musculus (house mouse); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 143188.27

構造登録者

Cowan, R.,Hall, G.,Carr, M. (登録日: 2022-10-12, 公開日: 2023-05-03, 最終更新日: 2024-11-13)

主引用文献

Cowan, R.,Trokter, M.,Oleksy, A.,Fedorova, M.,Sawmynaden, K.,Worzfeld, T.,Offermanns, S.,Matthews, D.,Carr, M.D.,Hall, G.
Nanobody inhibitors of Plexin-B1 identify allostery in plexin-semaphorin interactions and signaling.
J.Biol.Chem., 299:104740-104740, 2023

PubMed Abstract: 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.

PubMed: 37088134
DOI: 10.1016/j.jbc.2023.104740

実験手法

X-RAY DIFFRACTION (2.95 Å)