Complex structures of Rsu1 and PINCH1 reveal a regulatory mechanism of the ILK/PINCH/Parvin complex for F-actin dynamics
Abstract
Communications between actin filaments and integrin-mediated focal adhesion (FA) are crucial for cell adhesion and migration. As a core platform to organize FA proteins, the tripartite ILK/PINCH/Parvin (IPP) complex interacts with actin filaments to regulate the cytoskeleton-FA crosstalk. Rsu1, a Ras suppressor, is enriched in FA through PINCH1 and plays important roles in regulating F-actin structures. Here, we solved crystal structures of the Rsu1/PINCH1 complex, in which the Leucine-Rich-Repeats of Rsu1 form a solenoid structure to tightly associate with the C-terminal region of PINCH1. Further structural analysis uncovered that the interaction between Rsu1 and PINCH1 blocks the IPP-mediated F-actin bundling by disrupting the binding of PINCH1 to actin. Consistently, overexpressing Rsu1 in HeLa cells impairs stress fiber formation and cell spreading. Together, our findings demonstrated that Rsu1 is critical for tuning the communication between F-actin and FA by interacting with the IPP complex and negatively modulating the F-actin bundling.
Data availability
Diffraction data have been deposited in PDB under the accession code 7D2S, 7D2T and 7D2U.
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Crystal structure of Rsu1/PINCH1_LIM5C complexRCSB Protein data bank, 7D2S.
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Crystal structure of Rsu1/PINCH1_LIM45C complexRCSB Protein data bank, 7D2T.
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Crystal structure of Rsu1/PINCH1_LIM45C complexRCSB Protein data bank, 7D2U.
Article and author information
Author details
Funding
National Natural Science Foundation of China (31870757)
- Cong Yu
National Natural Science Foundation of China (31970741)
- Zhiyi Wei
National Natural Science Foundation of China (31770791)
- Zhiyi Wei
Science and Technology Planning Project of Guangdong Province (2017B030301018)
- Cong Yu
Shenzhen-Hong Kong Institute of Brain Science, Shenzhen Fundamental Research Institutions (2019SHIBS0002)
- Zhiyi Wei
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Reinhard Fässler, Max Planck Institute of Biochemistry, Germany
Version history
- Received: October 27, 2020
- Accepted: February 12, 2021
- Accepted Manuscript published: February 15, 2021 (version 1)
- Version of Record published: February 26, 2021 (version 2)
- Version of Record updated: March 8, 2021 (version 3)
Copyright
© 2021, Yang et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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