5L7N

Plexin A1 extracellular fragment, domains 7-10 (IPT3-IPT6)

Summary for 5L7N

• Entry DOI: 10.2210/pdb5l7n/pdb
• Descriptor: Plexin-A1, 2-acetamido-2-deoxy-beta-D-glucopyranose, 1,2-ETHANEDIOL, ... (5 entities in total)
• Functional Keywords: ipt domain, signaling protein, receptor, axon guidance
• Biological source: Mus musculus (Mouse)
• Cellular location: Cell membrane; Single-pass type I membrane protein: P70206
• Total number of polymer chains: 1
• Total formula weight: 43760.52

Authors

Kong, Y.,Janssen, B.J.C.,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. (deposition date: 2016-06-03, release date: 2017-03-15, Last modification date: 2024-10-23)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.2 Å)