Complex structures of Rsu1 and PINCH1 reveal a regulatory mechanism of the ILK/PINCH/Parvin complex for F-actin dynamics

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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.

The following data sets were generated

1. Yang H
2. Wei Z
3. Cong Y
(2020) Crystal structure of Rsu1/PINCH1_LIM5C complex
RCSB Protein data bank, 7D2S.

https://www.rcsb.org/structure/7D2S
1. Yang H
2. Wei Z
3. Cong Y
(2020) Crystal structure of Rsu1/PINCH1_LIM45C complex
RCSB Protein data bank, 7D2T.

https://www.rcsb.org/structure/7D2T
1. Yang H
2. Wei Z
3. Cong Y
(2020) Crystal structure of Rsu1/PINCH1_LIM45C complex
RCSB Protein data bank, 7D2U.

https://www.rcsb.org/structure/7D2U

Article and author information

Author details

Haibin Yang

Department of Biology, Southern University of Science and Technology, China, Shenzhen, China

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-6902-6941
Leishu Lin

Department of Biology, Southern University of Science and Technology, China, Shenzhen, China

Competing interests
The authors declare that no competing interests exist.
Kan Sun

Department of Biology, Southern University of Science and Technology, China, Shenzhen, China

Competing interests
The authors declare that no competing interests exist.
Ting Zhang

Department of Biology, Southern University of Science and Technology, China, Shenzhen, China

Competing interests
The authors declare that no competing interests exist.
Wan Chen

Department of Biology, Southern University of Science and Technology, China, Shenzhen, China

Competing interests
The authors declare that no competing interests exist.
Lianghui Li

Department of Biology, Southern University of Science and Technology, China, Shenzhen, China

Competing interests
The authors declare that no competing interests exist.
Yuchen Xie

Department of Biology, Southern University of Science and Technology, China, Shenzhen, China

Competing interests
The authors declare that no competing interests exist.
Chuanyue Wu

Department of Pathology, University of Pittsburgh, Pittsburgh, United States

For correspondence
carywu@pitt.edu

Competing interests
The authors declare that no competing interests exist.
Zhiyi Wei

Department of Biology, Southern University of Science and Technology, China, Shenzhen, China

For correspondence
weizy@sustech.edu.cn

Competing interests
The authors declare that no competing interests exist.
Cong Yu

Department of Biology, Southern University of Science and Technology, China, Shenzhen, China

For correspondence
yuc@sustech.edu.cn

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-2912-6347

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.

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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.