Cryo-electron tomography structure of Arp2/3 complex in cells reveals new insights into the branch junction

Fäßler, Florian; Dimchev, Georgi A; Hodirnau, Victor-Valentin; Wan, William; Schur, Florian KM

Cryo-electron tomography structure of Arp2/3 complex in cells reveals new insights into the branch junction

Fäßler F, Dimchev GA, Hodirnau V-V, Wan W, Schur FK. 2020. Cryo-electron tomography structure of Arp2/3 complex in cells reveals new insights into the branch junction. Nature Communications. 11, 6437.

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DOI

10.1038/s41467-020-20286-x

Journal Article | Published | English

Scopus indexed

Author

Fäßler, Florian^ISTA ; Dimchev, Georgi A^ISTA ; Hodirnau, Victor-Valentin^ISTA; Wan, William; Schur, Florian^ISTA

Department

Schur Group
Electron Microscopy Facility

Grant

Structure and isoform diversity of the Arp2/3 complex
Protein structure and function in filopodia across scales

Abstract

The actin-related protein (Arp)2/3 complex nucleates branched actin filament networks pivotal for cell migration, endocytosis and pathogen infection. Its activation is tightly regulated and involves complex structural rearrangements and actin filament binding, which are yet to be understood. Here, we report a 9.0 Å resolution structure of the actin filament Arp2/3 complex branch junction in cells using cryo-electron tomography and subtomogram averaging. This allows us to generate an accurate model of the active Arp2/3 complex in the branch junction and its interaction with actin filaments. Notably, our model reveals a previously undescribed set of interactions of the Arp2/3 complex with the mother filament, significantly different to the previous branch junction model. Our structure also indicates a central role for the ArpC3 subunit in stabilizing the active conformation.

Keywords

General Biochemistry; Genetics and Molecular Biology; General Physics and Astronomy; General Chemistry

Publishing Year

2020

Date Published

2020-12-22

Journal Title

Nature Communications

Acknowledgement

This research was supported by the Scientific Service Units (SSUs) of IST Austria through resources provided by Scientific Computing (SciComp), the Life Science Facility (LSF), the BioImaging Facility (BIF), and the Electron Microscopy Facility (EMF). We also thank Dimitry Tegunov (MPI for Biophysical Chemistry) for helpful discussions about the M software, and Michael Sixt (IST Austria) and Klemens Rottner (Technical University Braunschweig, HZI Braunschweig) for critical reading of the manuscript. We also thank Gregory Voth (University of Chicago) for providing us the MD-derived branch junction model for comparison. The authors acknowledge support from IST Austria and from the Austrian Science Fund (FWF): M02495 to G.D. and Austrian Science Fund (FWF): P33367 to F.K.M.S.

Acknowledged SSUs

Scientific Computing
Lab Support Facility
Imaging & Optics Facility
Electron Microscopy Facility

Volume

Article Number

6437

ISSN

2041-1723

IST-REx-ID

8971

Cite this

Fäßler F, Dimchev GA, Hodirnau V-V, Wan W, Schur FK. Cryo-electron tomography structure of Arp2/3 complex in cells reveals new insights into the branch junction. Nature Communications. 2020;11. doi:10.1038/s41467-020-20286-x

Fäßler, F., Dimchev, G. A., Hodirnau, V.-V., Wan, W., & Schur, F. K. (2020). Cryo-electron tomography structure of Arp2/3 complex in cells reveals new insights into the branch junction. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-020-20286-x

Fäßler, Florian, Georgi A Dimchev, Victor-Valentin Hodirnau, William Wan, and Florian KM Schur. “Cryo-Electron Tomography Structure of Arp2/3 Complex in Cells Reveals New Insights into the Branch Junction.” Nature Communications. Springer Nature, 2020. https://doi.org/10.1038/s41467-020-20286-x.

F. Fäßler, G. A. Dimchev, V.-V. Hodirnau, W. Wan, and F. K. Schur, “Cryo-electron tomography structure of Arp2/3 complex in cells reveals new insights into the branch junction,” Nature Communications, vol. 11. Springer Nature, 2020.

Fäßler, Florian, et al. “Cryo-Electron Tomography Structure of Arp2/3 Complex in Cells Reveals New Insights into the Branch Junction.” Nature Communications, vol. 11, 6437, Springer Nature, 2020, doi:10.1038/s41467-020-20286-x.

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