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Opening of tandem calponin homology domains regulates their affinity for F-actin

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Abstract

Many actin-binding proteins contain calponin homology (CH) domains, but the manner in which these domains interact with F-actin has been controversial. Crystal structures have shown the tandem CH domains of α-actinin to be in a compact, closed conformation, but the interpretations of complexes of such tandem CH domains with F-actin have been ambiguous. We show that the tandem CH domains of α-actinin bind F-actin in an open conformation, explaining mutations that cause human diseases and suggesting that the opening of these domains may be one of the main regulatory mechanisms for proteins with tandem CH domains.

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Figure 1: Electron microscopy of complexes.
Figure 2: Pseudoatomic models.
Figure 3: Steric clash between CH2 of α-actinin and actin.

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Acknowledgements

This work was supported by US National Institutes of Health grant GM081303 (to E.H.E.) and by Austrian Science Fund grant P19060 (to K.D.-C.).

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Authors and Affiliations

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

    Vitold E Galkin, Albina Orlova & Edward H Egelman

  2. Department for Structural and Computational Biology, Max F. Perutz Laboratories, University of Vienna, Campus Vienna Biocenter 5, Vienna, Austria.,

    Anita Salmazo & Kristina Djinovic-Carugo

  3. Department of Biochemistry, Faculty of Chemistry and Chemical Technology, University of Ljubljana, Ljubljana, Slovenia

    Kristina Djinovic-Carugo

Authors
  1. Vitold E Galkin
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  2. Albina Orlova
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  3. Anita Salmazo
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  4. Kristina Djinovic-Carugo
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  5. Edward H Egelman
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Contributions

A.S. and A.O. performed sample preparations; A.O. did the electron microscopy; V.E.G. performed the image analysis and model building; V.E.G., A.O., E.H.E. and K.D.-C. prepared the manuscript.

Corresponding author

Correspondence to Edward H Egelman.

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The authors declare no competing financial interests.

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Supplementary Methods and Supplementary Figure 1 (PDF 1785 kb)

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Galkin, V., Orlova, A., Salmazo, A. et al. Opening of tandem calponin homology domains regulates their affinity for F-actin. Nat Struct Mol Biol 17, 614–616 (2010). https://doi.org/10.1038/nsmb.1789

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