5XNQ

Crystal structures of human SALM5

Summary for 5XNQ

• Entry DOI: 10.2210/pdb5xnq/pdb
• Descriptor: Leucine-rich repeat and fibronectin type-III domain-containing protein 5, 2-acetamido-2-deoxy-beta-D-glucopyranose, SODIUM ION, ... (7 entities in total)
• Functional Keywords: regulating some neural developments, membrane protein
• Biological source: Homo sapiens (Human)
• Cellular location: Membrane ; Single-pass type I membrane protein : Q96NI6
• Total number of polymer chains: 1
• Total formula weight: 42241.10

Authors

Liu, H.,Lin, Z.,Xu, F. (deposition date: 2017-05-24, release date: 2018-01-24, Last modification date: 2024-11-06)

Primary citation

Lin, Z.,Liu, J.,Ding, H.,Xu, F.,Liu, H.
Structural basis of SALM5-induced PTP delta dimerization for synaptic differentiation
Nat Commun, 9:268-268, 2018

PubMed Abstract: SALM5, a synaptic adhesion molecule implicated in autism, induces presynaptic differentiation through binding to the LAR family receptor protein tyrosine phosphatases (LAR-RPTPs) that have been highlighted as presynaptic hubs for synapse formation. The mechanisms underlying SALM5/LAR-RPTP interaction remain unsolved. Here we report crystal structures of human SALM5 LRR-Ig alone and in complex with human PTPδ Ig1-3 (MeA). Distinct from other LAR-RPTP ligands, SALM5 mainly exists as a dimer with LRR domains from two protomers packed in an antiparallel fashion. In the 2:2 heterotetrameric SALM5/PTPδ complex, a SALM5 dimer bridges two separate PTPδ molecules. Structure-guided mutations and heterologous synapse formation assays demonstrate that dimerization of SALM5 is prerequisite for its functionality in inducing synaptic differentiation. This study presents a structural template for the SALM family and reveals a mechanism for how a synaptic adhesion molecule directly induces cis-dimerization of LAR-RPTPs into higher-order signaling assembly.

PubMed: 29348579
DOI: 10.1038/s41467-017-02414-2

Experimental method

X-RAY DIFFRACTION (2.802 Å)