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

Sakesit Chumnarnsilpa, Robert C. Robinson, Jonathan M. Grimes, Cedric Leyrat

Research output: Contribution to journalArticle

5 Citations (Scopus)

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 Ca 2+ -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 Ca 2+ -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 Ca 2+ -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 Ca 2+ -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.

Original languageEnglish
Article number8254
JournalNature communications
Volume6
DOIs
Publication statusPublished - Sep 14 2015
Externally publishedYes

Fingerprint

calcium
Gelsolin
Calcium
Conformations
Microfilament Proteins
destabilization
Molecular Dynamics Simulation
mutations
X ray scattering
varespladib methyl
Molecular dynamics
scinderin
Actins
Crystal structure
Chemical activation
Binding Sites
X-Rays
activation
molecular dynamics
proteins

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Calcium-controlled conformational choreography in the N-terminal half of adseverin. / Chumnarnsilpa, Sakesit; Robinson, Robert C.; Grimes, Jonathan M.; Leyrat, Cedric.

In: Nature communications, Vol. 6, 8254, 14.09.2015.

Research output: Contribution to journalArticle

Chumnarnsilpa, Sakesit ; Robinson, Robert C. ; Grimes, Jonathan M. ; Leyrat, Cedric. / Calcium-controlled conformational choreography in the N-terminal half of adseverin. In: Nature communications. 2015 ; Vol. 6.
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