6l03 | pdb_00006l03

structure of PTP-MEG2 and MUNC18-1-pY145 peptide complex

spinqualitylabelsall models 6l03, resolution 2.08Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6l03 is a 2 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 2.084Å Ligands: PTR Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PTN9_HUMAN Protein-tyrosine phosphatase that could participate in the transfer of hydrophobic ligands or in functions of the Golgi apparatus. Publication Abstract from PubMed Tyrosine phosphorylation of secretion machinery proteins is a crucial regulatory mechanism for exocytosis. However, the participation of protein tyrosine phosphatases (PTPs) in different exocytosis stages has not been defined. Here we demonstrate that PTP-MEG2 controls multiple steps of catecholamine secretion. Biochemical and crystallographic analyses reveal key residues that govern the interaction between PTP-MEG2 and its substrate, a peptide containing the phosphorylated NSF-pY(83) site, specify PTP-MEG2 substrate selectivity, and modulate the fusion of catecholamine-containing vesicles. Unexpectedly, delineation of PTP-MEG2 mutants along with the NSF binding interface reveals that PTP-MEG2 controls the fusion pore opening through NSF independent mechanisms. Utilizing bioinformatics search and biochemical and electrochemical screening approaches, we uncover that PTP-MEG2 regulates the opening and extension of the fusion pore by dephosphorylating the DYNAMIN2-pY(125) and MUNC18-1-pY(145) sites. Further structural and biochemical analyses confirmed the interaction of PTP-MEG2 with MUNC18-1-pY(145) or DYNAMIN2-pY(125) through a distinct structural basis compared with that of the NSF-pY(83) site. Our studies thus provide mechanistic insights in complex exocytosis processes. PTP-MEG2 regulates quantal size and fusion pore opening through two distinct structural bases and substrates.,Xu YF, Chen X, Yang Z, Xiao P, Liu CH, Li KS, Yang XZ, Wang YJ, Zhu ZL, Xu ZG, Zhang S, Wang C, Song YC, Zhao WD, Wang CH, Ji ZL, Zhang ZY, Cui M, Sun JP, Yu X EMBO Rep. 2021 May 5;22(5):e52141. doi: 10.15252/embr.202052141. Epub 2021 Mar , 25. PMID:33764618 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Tyrosine phosphatase 3D structures

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