5L5C

Plexin A1 full extracellular region, domains 1 to 10, to 6 angstrom, spacegroup P4(3)2(1)2

5L5C の概要

• エントリーDOI: 10.2210/pdb5l5c/pdb
• 分子名称: Plexin-A1, alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose-(1-3)-alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• 機能のキーワード: receptor, signaling, axon guidance, signaling protein
• 由来する生物種: Mus musculus (House Mouse)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 140943.13

構造登録者

Janssen, B.J.C.,Kong, Y.,Malinauskas, T.,Vangoor, V.R.,Coles, C.H.,Kaufmann, R.,Ni, T.,Gilbert, R.J.C.,Padilla-Parra, S.,Pasterkamp, R.J.,Jones, E.Y. (登録日: 2016-05-28, 公開日: 2016-07-06, 最終更新日: 2024-10-23)

主引用文献

Kong, Y.,Janssen, B.J.,Malinauskas, T.,Vangoor, V.R.,Coles, C.H.,Kaufmann, R.,Ni, T.,Gilbert, R.J.,Padilla-Parra, S.,Pasterkamp, R.J.,Jones, E.Y.
Structural Basis for Plexin Activation and Regulation.
Neuron, 91:548-560, 2016

PubMed Abstract: Class A plexins (PlxnAs) act as semaphorin receptors and control diverse aspects of nervous system development and plasticity, ranging from axon guidance and neuron migration to synaptic organization. PlxnA signaling requires cytoplasmic domain dimerization, but extracellular regulation and activation mechanisms remain unclear. Here we present crystal structures of PlxnA (PlxnA1, PlxnA2, and PlxnA4) full ectodomains. Domains 1-9 form a ring-like conformation from which the C-terminal domain 10 points away. All our PlxnA ectodomain structures show autoinhibitory, intermolecular "head-to-stalk" (domain 1 to domain 4-5) interactions, which are confirmed by biophysical assays, live cell fluorescence microscopy, and cell-based and neuronal growth cone collapse assays. This work reveals a 2-fold role of the PlxnA ectodomains: imposing a pre-signaling autoinhibitory separation for the cytoplasmic domains via intermolecular head-to-stalk interactions and supporting dimerization-based PlxnA activation upon ligand binding. More generally, our data identify a novel molecular mechanism for preventing premature activation of axon guidance receptors.

PubMed: 27397516
DOI: 10.1016/j.neuron.2016.06.018

実験手法

X-RAY DIFFRACTION (6 Å)