3WUU

Structure basis of inactivating cell abscission with chimera peptide 1

3WUU の概要

• エントリーDOI: 10.2210/pdb3wuu/pdb
• 関連するPDBエントリー: 3WUT 3WUV
• 分子名称: Centrosomal protein of 55 kDa, TEX-14 (3 entities in total)
• 機能のキーワード: coiled-coil, cell cycle
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm, cytoskeleton, microtubule organizing center, centrosome, centriole: Q53EZ4; Cytoplasm : Q8IWB6
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 63796.09

構造登録者

Kim, H.J.,Matsuura, A.,Lee, H.H. (登録日: 2014-05-05, 公開日: 2015-07-15, 最終更新日: 2024-05-29)

主引用文献

Kim, H.J.,Yoon, J.,Matsuura, A.,Na, J.H.,Lee, W.K.,Kim, H.,Choi, J.W.,Park, J.E.,Park, S.J.,Kim, K.T.,Chang, R.,Lee, B.I.,Yu, Y.G.,Shin, Y.K.,Jeong, C.,Rhee, K.,Lee, H.H.
Structural and biochemical insights into the role of testis-expressed gene 14 (TEX14) in forming the stable intercellular bridges of germ cells.
Proc.Natl.Acad.Sci.USA, 112:12372-12377, 2015

PubMed Abstract: 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.

PubMed: 26392564
DOI: 10.1073/pnas.1418606112

実験手法

X-RAY DIFFRACTION (2.904 Å)