6DCE

X-ray structure of FIP200 claw domain

Summary for 6DCE

• Entry DOI: 10.2210/pdb6dce/pdb
• Descriptor: RB1-inducible coiled-coil protein 1, SULFATE ION (3 entities in total)
• Functional Keywords: autophagy, fip200, structural protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 11905.56

Authors

Su, M.-Y.,Hurley, J.H. (deposition date: 2018-05-05, release date: 2019-03-06, Last modification date: 2019-05-01)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.56 Å)