5L5N: Plexin A4 Full Extracellular Region, Domains 1 To 7 Modeled, Data To 8.5 Angstrom, Spacegroup P4(3)22

Citation:
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.
PDB ID: 5L5NDownload
MMDB ID: 140907
PDB Deposition Date: 2016/5/28
Updated in MMDB: 2016/08
Experimental Method:
x-ray diffraction
Resolution: 8.5  Å
Source Organism:
Similar Structures:
Biological Unit for 5L5N: dimeric; determined by author
Molecular Components in 5L5N
Label Count Molecule
Proteins (2 molecules)
2
Plexin-a4(Gene symbol: Plxna4)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

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