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Structural polymorphism in F-actin

Nature Structural & Molecular Biology volume 17, pages 1318–1323 (2010)Cite this article

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Abstract

Actin has maintained an exquisite degree of sequence conservation over large evolutionary distances for reasons that are not understood. The desire to explain phenomena from muscle contraction to cytokinesis in mechanistic detail has driven the generation of an atomic model of the actin filament (F-actin). Here we use electron cryomicroscopy to show that frozen-hydrated actin filaments contain a multiplicity of different structural states. We show (at ∼10 Å resolution) that subdomain 2 can be disordered and can make multiple contacts with the C terminus of a subunit above it. We link a number of disease-causing mutations in the human ACTA1 gene to the most structurally dynamic elements of actin. Because F-actin is structurally polymorphic, it cannot be described using only one atomic model and must be understood as an ensemble of different states.

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Figure 1: Six structural modes of actin found in frozen-hydrated actin filaments.
Figure 2: D loop of the lower subunit makes polymorphic interactions with the upper protomer.
Figure 3: D loop may work as an allosteric switch.
Figure 4: The structural states of SD2 and the ATP-binding cleft are coupled.
Figure 5: Mutations in the ACTA1 gene causing human disease map to either the intersubunit contacts or mobile elements of actin.

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Acknowledgements

This work was supported by a grant from the US National Institutes of Health (NIH GM081303 to E.H.E.).

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, Virginia, USA

    Vitold E Galkin, Albina Orlova & Edward H Egelman

  2. Institute of Structural Biology and Biophysics, Jülich, Forschungszentrum Jülich, Germany

    Gunnar F Schröder

Authors
  1. Vitold E Galkin
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  2. Albina Orlova
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  3. Gunnar F Schröder
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  4. Edward H Egelman
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Contributions

A.O. prepared specimens and EM; V.E.G. analyzed images, made classifications, created three-dimensional reconstructions, and built preliminary models; R.S. built and refined models; V.E.G., A.O. and E.H.E. discussed the data and wrote the paper.

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Correspondence to Vitold E Galkin or Edward H Egelman.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–5 and Supplementary Methods (PDF 834 kb)

Supplementary Video 1

When the power spectra derived from the raw images of mode 1 and mode 5 classes are superimposed, significant changes in the position and relative intensities of layer line maxima are evident. (GIF 89 kb)

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Galkin, V., Orlova, A., Schröder, G. et al. Structural polymorphism in F-actin. Nat Struct Mol Biol 17, 1318–1323 (2010). https://doi.org/10.1038/nsmb.1930

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