3wuv

Structure basis of inactivating cell abscission with chimera peptide 2

spinqualitylabelsall models 3wuv, resolution 2.79Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3wuv is a 18 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 2.79Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function CEP55_HUMAN Plays a role in mitotic exit and cytokinesis. Not required for microtubule nucleation. Recruits PDCD6IP and TSG101 to midbody during cytokinesis. Publication Abstract from PubMed Intercellular bridges are a conserved feature of spermatogenesis in mammalian germ cells and derive from arresting cell abscission at the final stage of cytokinesis. However, it remains to be fully understood how germ cell abscission is arrested in the presence of general cytokinesis components. The TEX14 (testis-expressed gene 14) protein is recruited to the midbody and plays a key role in the inactivation of germ cell abscission. To gain insights into the structural organization of TEX14 at the midbody, we have determined the crystal structures of the EABR [endosomal sorting complex required for transport (ESCRT) and ALIX-binding region] of CEP55 bound to the TEX14 peptide (or its chimeric peptides) and performed functional characterization of the CEP55-TEX14 interaction by multiexperiment analyses. We show that TEX14 interacts with CEP55-EABR via its AxGPPx3Y (Ala793, Gly795, Pro796, Pro797, and Tyr801) and PP (Pro803 and Pro804) sequences, which together form the AxGPPx3YxPP motif. TEX14 competitively binds to CEP55-EABR to prevent the recruitment of ALIX, which is a component of the ESCRT machinery with the AxGPPx3Y motif. We also demonstrate that a high affinity and a low dissociation rate of TEX14 to CEP55, and an increase in the local concentration of TEX14, cooperatively prevent ALIX from recruiting ESCRT complexes to the midbody. The action mechanism of TEX14 suggests a scheme of how to inactivate the abscission of abnormal cells, including cancer cells. Structural and biochemical insights into the role of testis-expressed gene 14 (TEX14) in forming the stable intercellular bridges of germ cells.,Kim HJ, Yoon J, Matsuura A, Na JH, Lee WK, Kim H, Choi JW, Park JE, Park SJ, Kim KT, Chang R, Lee BI, Yu YG, Shin YK, Jeong C, Rhee K, Lee HH Proc Natl Acad Sci U S A. 2015 Sep 21. pii: 201418606. PMID:26392564 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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