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

Open access
Turco, Eleonora, Witt, Marie, Abert, Christine, Bock-Bierbaum, Tobias, Su, Ming-Yuan, Trapannone, Riccardo, Sztacho, Martin, Danieli, Alberto, Shi, Xiaoshan, Zaffagnini, Gabriele, Gamper, Annamaria, Schuschnig, Martina, Fracchiolla, Dorotea, Bernklau, Daniel, Romanov, Julia, Hartl, Markus, Hurley, James H., Daumke, Oliver, Martens, Sascha·2019·Molecular Cell

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.

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Metadata

Authors
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.
Venue
Molecular Cell
Publisher
Elsevier BV
Published
2019-04
Volume
74
Issue
2
Pages
330-346.e11
ISSN
1097-2765 (ISSN-L)
OpenAlex
W2918672868
Cited by
338
References
11
FWCI
26.83
Type
journal article
Language
en
Open access
hybrid

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The paper
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. (2019). FIP200 Claw Domain Binding to p62 Promotes Autophagosome Formation at Ubiquitin Condensates. Molecular Cell. https://doi.org/10.1016/j.molcel.2019.01.035

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.