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

  1. Haibin Yang
  2. Leishu Lin
  3. Kan Sun
  4. Ting Zhang
  5. Wan Chen
  6. Lianghui Li
  7. Yuchen Xie
  8. Chuanyue Wu  Is a corresponding author
  9. Zhiyi Wei  Is a corresponding author
  10. Cong Yu  Is a corresponding author
  1. Southern University of Science and Technology, China, China
  2. University of Pittsburgh, United States

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

Article and author information

Author details

  1. Haibin Yang

    Department of Biology, Southern University of Science and Technology, China, Shenzhen, China
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6902-6941
  2. Leishu Lin

    Department of Biology, Southern University of Science and Technology, China, Shenzhen, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Kan Sun

    Department of Biology, Southern University of Science and Technology, China, Shenzhen, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Ting Zhang

    Department of Biology, Southern University of Science and Technology, China, Shenzhen, China
    Competing interests
    The authors declare that no competing interests exist.
  5. Wan Chen

    Department of Biology, Southern University of Science and Technology, China, Shenzhen, China
    Competing interests
    The authors declare that no competing interests exist.
  6. Lianghui Li

    Department of Biology, Southern University of Science and Technology, China, Shenzhen, China
    Competing interests
    The authors declare that no competing interests exist.
  7. Yuchen Xie

    Department of Biology, Southern University of Science and Technology, China, Shenzhen, China
    Competing interests
    The authors declare that no competing interests exist.
  8. 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.
  9. 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.
  10. 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.
    ORCID icon "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.

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.

Metrics

  • 1,394
    views
  • 223
    downloads
  • 11
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Haibin Yang
  2. Leishu Lin
  3. Kan Sun
  4. Ting Zhang
  5. Wan Chen
  6. Lianghui Li
  7. Yuchen Xie
  8. Chuanyue Wu
  9. Zhiyi Wei
  10. Cong Yu
(2021)
Complex structures of Rsu1 and PINCH1 reveal a regulatory mechanism of the ILK/PINCH/Parvin complex for F-actin dynamics
eLife 10:e64395.
https://doi.org/10.7554/eLife.64395

Share this article

https://doi.org/10.7554/eLife.64395

Further reading

    1. Biochemistry and Chemical Biology
    2. Microbiology and Infectious Disease
    Lina Antenucci, Salla Virtanen ... Perttu Permi
    Research Article

    Orchestrated action of peptidoglycan (PG) synthetases and hydrolases is vital for bacterial growth and viability. Although the function of several PG synthetases and hydrolases is well understood, the function, regulation, and mechanism of action of PG hydrolases characterised as lysostaphin-like endopeptidases have remained elusive. Many of these M23 family members can hydrolyse glycyl-glycine peptide bonds and show lytic activity against Staphylococcus aureus whose PG contains a pentaglycine bridge, but their exact substrate specificity and hydrolysed bonds are still vaguely determined. In this work, we have employed NMR spectroscopy to study both the substrate specificity and the bond cleavage of the bactericide lysostaphin and the S. aureus PG hydrolase LytM. Yet, we provide substrate-level evidence for the functional role of these enzymes. Indeed, our results show that the substrate specificities of these structurally highly homologous enzymes are similar, but unlike observed earlier both LytM and lysostaphin prefer the D-Ala-Gly cross-linked part of mature peptidoglycan. However, we show that while lysostaphin is genuinely a glycyl-glycine hydrolase, LytM can also act as a D-alanyl-glycine endopeptidase.

    1. Biochemistry and Chemical Biology
    2. Chromosomes and Gene Expression
    Ting-Wen Chen, Hsiao-Wei Liao ... Chung-Te Chang
    Research Article

    The mRNA 5'-cap structure removal by the decapping enzyme DCP2 is a critical step in gene regulation. While DCP2 is the catalytic subunit in the decapping complex, its activity is strongly enhanced by multiple factors, particularly DCP1, which is the major activator in yeast. However, the precise role of DCP1 in metazoans has yet to be fully elucidated. Moreover, in humans, the specific biological functions of the two DCP1 paralogs, DCP1a and DCP1b, remain largely unknown. To investigate the role of human DCP1, we generated cell lines that were deficient in DCP1a, DCP1b, or both to evaluate the importance of DCP1 in the decapping machinery. Our results highlight the importance of human DCP1 in decapping process and show that the EVH1 domain of DCP1 enhances the mRNA-binding affinity of DCP2. Transcriptome and metabolome analyses outline the distinct functions of DCP1a and DCP1b in human cells, regulating specific endogenous mRNA targets and biological processes. Overall, our findings provide insights into the molecular mechanism of human DCP1 in mRNA decapping and shed light on the distinct functions of its paralogs.