6kr4 | pdb_00006kr4

Crystal structure of the liprin-alpha3_SAM123/LAR_D1D2 complex

spinqualitylabelsall models 6kr4, resolution 2.85Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6kr4 is a 8 chain structure with sequence from Human and Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: P6G, PG4, PGE, PO4 Gene: PTPRF, LAR (HUMAN), Ppfia3 (LK3 transgenic mice) Activity: Protein-tyrosine-phosphatase, with EC number 3.1.3.48 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [PTPRF_HUMAN] Possible cell adhesion receptor. It possesses an intrinsic protein tyrosine phosphatase activity (PTPase). The first PTPase domain has enzymatic activity, while the second one seems to affect the substrate specificity of the first one. [LIPA3_MOUSE] May regulate the disassembly of focal adhesions. May localize receptor-like tyrosine phosphatases type 2A at specific sites on the plasma membrane, possibly regulating their interaction with the extracellular environment and their association with substrates (By similarity). Publication Abstract from PubMed Leukocyte 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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