5xwt
Crystal structure of PTPdelta Ig1-Fn1 in complex with SALM5 LRR-IgCrystal structure of PTPdelta Ig1-Fn1 in complex with SALM5 LRR-Ig
Structural highlights
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 PubMedSynapse formation is triggered by trans-synaptic interactions of cell adhesion molecules, termed synaptic organizers. Three members of type-II receptor protein tyrosine phosphatases (classified as type-IIa RPTPs; PTPdelta, PTPsigma and LAR) are known as presynaptic organizers. Synaptic adhesion-like molecules (SALMs) have recently emerged as a family of postsynaptic organizers. Although all five SALM isoforms can bind to the type-IIa RPTPs, only SALM3 and SALM5 reportedly have synaptogenic activities depending on their binding. Here, we report the crystal structures of apo-SALM5, and PTPdelta-SALM2 and PTPdelta-SALM5 complexes. The leucine-rich repeat (LRR) domains of SALMs interact with the second immunoglobulin-like (Ig) domain of PTPdelta, whereas the Ig domains of SALMs interact with both the second and third Ig domains of PTPdelta. Unexpectedly, the structures exhibit the LRR-mediated 2:2 complex. Our synaptogenic co-culture assay using site-directed SALM5 mutants demonstrates that presynaptic differentiation induced by PTPdelta-SALM5 requires the dimeric property of SALM5. Structural basis of trans-synaptic interactions between PTPdelta and SALMs for inducing synapse formation.,Goto-Ito S, Yamagata A, Sato Y, Uemura T, Shiroshima T, Maeda A, Imai A, Mori H, Yoshida T, Fukai S Nat Commun. 2018 Jan 18;9(1):269. doi: 10.1038/s41467-017-02417-z. PMID:29348429[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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