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Calcium-controlled conformational choreography in the N-terminal half of adseverin

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  • Sakesit Chumnarnsilpa

    (University of Oxford, Henry Wellcome Building for Genomic Medicine
    Institute of Molecular and Cell Biology, A*STAR (Agency for Science, Technology and Research)
    School of Biochemistry, Institute of Science, Suranaree University of Technology)

  • Robert C. Robinson

    (Institute of Molecular and Cell Biology, A*STAR (Agency for Science, Technology and Research)
    National University of Singapore)

  • Jonathan M. Grimes

    (University of Oxford, Henry Wellcome Building for Genomic Medicine
    Diamond Light Source Ltd)

  • Cedric Leyrat

    (University of Oxford, Henry Wellcome Building for Genomic Medicine)

Abstract

Adseverin is a member of the calcium-regulated gelsolin superfamily of actin-binding proteins. Here we report the crystal structure of the calcium-free N-terminal half of adseverin (iA1–A3) and the Ca2+-bound structure of A3, which reveal structural similarities and differences with gelsolin. Solution small-angle X-ray scattering combined with ensemble optimization revealed a dynamic Ca2+-dependent equilibrium between inactive, intermediate and active conformations. Increasing calcium concentrations progressively shift this equilibrium from a main population of inactive conformation to the active form. Molecular dynamics simulations of iA1–A3 provided insights into Ca2+-induced destabilization, implicating a critical role for the A2 type II calcium-binding site and the A2A3 linker in the activation process. Finally, mutations that disrupt the A1/A3 interface increase Ca2+-independent F-actin severing by A1–A3, albeit at a lower efficiency than observed for gelsolin domains G1–G3. Together, these data address the calcium dependency of A1–A3 activity in relation to the calcium-independent activity of G1–G3.

Suggested Citation

  • Sakesit Chumnarnsilpa & Robert C. Robinson & Jonathan M. Grimes & Cedric Leyrat, 2015. "Calcium-controlled conformational choreography in the N-terminal half of adseverin," Nature Communications, Nature, vol. 6(1), pages 1-13, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9254
    DOI: 10.1038/ncomms9254
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    Cited by:

    1. Takayoshi Matsumura & Haruhito Totani & Yoshitaka Gunji & Masahiro Fukuda & Rui Yokomori & Jianwen Deng & Malini Rethnam & Chong Yang & Tze King Tan & Tadayoshi Karasawa & Kazuomi Kario & Masafumi Tak, 2022. "A Myb enhancer-guided analysis of basophil and mast cell differentiation," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

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