6kr4
Crystal structure of the liprin-alpha3_SAM123/LAR_D1D2 complex
Structural highlights
FunctionPTPRF_HUMAN Possible cell adhesion receptor. It possesses an intrinsic protein tyrosine phosphatase activity (PTPase).[1] The first PTPase domain has enzymatic activity, while the second one seems to affect the substrate specificity of the first one.[2] Publication Abstract from PubMedLeukocyte common antigen-related receptor protein tyrosine phosphatases (LAR-RPTPs) are cell adhesion molecules involved in mediating neuronal development. The binding of LAR-RPTPs to extracellular ligands induces local clustering of LAR-RPTPs to regulate axon growth and synaptogenesis. LAR-RPTPs interact with synaptic liprin-alpha proteins via the two cytoplasmic phosphatase domains, D1 and D2. Here we solve the crystal structure of LAR_D1D2 in complex with the SAM repeats of liprin-alpha3, uncovering a conserved two-site binding mode. Cellular analysis shows that liprin-alphas robustly promote clustering of LAR in cells by both the liprin-alpha/LAR interaction and the oligomerization of liprin-alpha. Structural analysis reveals a unique homophilic interaction of LAR via the catalytically active D1 domains. Disruption of the D1/D1 interaction diminishes the liprin-alpha-promoted LAR clustering and increases tyrosine dephosphorylation, demonstrating that the phosphatase activity of LAR is negatively regulated by forming clusters. Additionally, we find that the binding of LAR to liprin-alpha allosterically regulates the liprin-alpha/liprin-beta interaction. Structural basis of liprin-alpha-promoted LAR-RPTP clustering for modulation of phosphatase activity.,Xie X, Luo L, Liang M, Zhang W, Zhang T, Yu C, Wei Z Nat Commun. 2020 Jan 10;11(1):169. doi: 10.1038/s41467-019-13949-x. PMID:31924785[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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