6DCE

X-ray structure of FIP200 claw domain

6DCE の概要

• エントリーDOI: 10.2210/pdb6dce/pdb
• 分子名称: RB1-inducible coiled-coil protein 1, SULFATE ION (3 entities in total)
• 機能のキーワード: autophagy, fip200, structural protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 11905.56

構造登録者

Su, M.-Y.,Hurley, J.H. (登録日: 2018-05-05, 公開日: 2019-03-06, 最終更新日: 2024-12-25)

主引用文献

Turco, E.,Witt, M.,Abert, C.,Bock-Bierbaum, T.,Su, M.Y.,Trapannone, R.,Sztacho, M.,Danieli, A.,Shi, X.,Zaffagnini, G.,Gamper, A.,Schuschnig, M.,Fracchiolla, D.,Bernklau, D.,Romanov, J.,Hartl, M.,Hurley, J.H.,Daumke, O.,Martens, S.
FIP200 Claw Domain Binding to p62 Promotes Autophagosome Formation at Ubiquitin Condensates.
Mol. Cell, 74:330-, 2019

PubMed Abstract: The autophagy cargo receptor p62 facilitates the condensation of misfolded, ubiquitin-positive proteins and their degradation by autophagy, but the molecular mechanism of p62 signaling to the core autophagy machinery is unclear. Here, we show that disordered residues 326-380 of p62 directly interact with the C-terminal region (CTR) of FIP200. Crystal structure determination shows that the FIP200 CTR contains a dimeric globular domain that we designated the "Claw" for its shape. The interaction of p62 with FIP200 is mediated by a positively charged pocket in the Claw, enhanced by p62 phosphorylation, mutually exclusive with the binding of p62 to LC3B, and it promotes degradation of ubiquitinated cargo by autophagy. Furthermore, the recruitment of the FIP200 CTR slows the phase separation of ubiquitinated proteins by p62 in a reconstituted system. Our data provide the molecular basis for a crosstalk between cargo condensation and autophagosome formation.

PubMed: 30853400
DOI: 10.1016/j.molcel.2019.01.035

実験手法

X-RAY DIFFRACTION (1.56 Å)