5xnq

Crystal structures of human SALM5Crystal structures of human SALM5

Structural highlights

5xnq is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.802Å
Ligands:	, , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

LRFN5_HUMAN Cell adhesion molecule that mediates homophilic cell-cell adhesion in a Ca(2+)-independent manner. Promotes neurite outgrowth in hippocampal neurons.^[1] ^[2]

Publication Abstract from PubMed

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 PTPdelta 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/PTPdelta complex, a SALM5 dimer bridges two separate PTPdelta 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.

Structural basis of SALM5-induced PTPdelta dimerization for synaptic differentiation.,Lin Z, Liu J, Ding H, Xu F, Liu H Nat Commun. 2018 Jan 18;9(1):268. doi: 10.1038/s41467-017-02414-2. PMID:29348579^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Seabold GK, Wang PY, Chang K, Wang CY, Wang YX, Petralia RS, Wenthold RJ. The SALM family of adhesion-like molecules forms heteromeric and homomeric complexes. J Biol Chem. 2008 Mar 28;283(13):8395-405. doi: 10.1074/jbc.M709456200. Epub 2008, Jan 28. PMID:18227064 doi:http://dx.doi.org/10.1074/jbc.M709456200
↑ Wang PY, Seabold GK, Wenthold RJ. Synaptic adhesion-like molecules (SALMs) promote neurite outgrowth. Mol Cell Neurosci. 2008 Sep;39(1):83-94. doi: 10.1016/j.mcn.2008.05.019. Epub, 2008 Jun 7. PMID:18585462 doi:http://dx.doi.org/10.1016/j.mcn.2008.05.019
↑ Lin Z, Liu J, Ding H, Xu F, Liu H. Structural basis of SALM5-induced PTPdelta dimerization for synaptic differentiation. Nat Commun. 2018 Jan 18;9(1):268. doi: 10.1038/s41467-017-02414-2. PMID:29348579 doi:http://dx.doi.org/10.1038/s41467-017-02414-2

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OCA

[1] Seabold GK, Wang PY, Chang K, Wang CY, Wang YX, Petralia RS, Wenthold RJ. The SALM family of adhesion-like molecules forms heteromeric and homomeric complexes. J Biol Chem. 2008 Mar 28;283(13):8395-405. doi: 10.1074/jbc.M709456200. Epub 2008, Jan 28. PMID:18227064 doi:http://dx.doi.org/10.1074/jbc.M709456200

[2] Wang PY, Seabold GK, Wenthold RJ. Synaptic adhesion-like molecules (SALMs) promote neurite outgrowth. Mol Cell Neurosci. 2008 Sep;39(1):83-94. doi: 10.1016/j.mcn.2008.05.019. Epub, 2008 Jun 7. PMID:18585462 doi:http://dx.doi.org/10.1016/j.mcn.2008.05.019

[3] Lin Z, Liu J, Ding H, Xu F, Liu H. Structural basis of SALM5-induced PTPdelta dimerization for synaptic differentiation. Nat Commun. 2018 Jan 18;9(1):268. doi: 10.1038/s41467-017-02414-2. PMID:29348579 doi:http://dx.doi.org/10.1038/s41467-017-02414-2

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