FIP200 Claw Domain Binding to p62 Promotes Autophagosome Formation at Ubiquitin Condensates

• DOI: 10.1016/j.molcel.2019.01.035
• Publication Date: 2019-03-07T15:56:06Z
• Authors: Eleonora Turco; Marie Witt; Christine Abert; Tobias Bock-Bierbaum; Ming-Yuan Su; Riccardo Trapannone; Martin Sztacho; Alberto Danieli; Xiaoshan Shi; Gabriele Zaffagnini; Annamaria Gamper; Martina Schuschnig; Dorotea Fracchiolla; Daniel Bernklau; Julia Romanov; Markus Hartl; James H. Hurley; Oliver Daumke; Sascha Martens
• Keywords: Claw; Autophagosome

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