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PDBsum entry 5a1m
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Actin-binding protein
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PDB id
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5a1m
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References listed in PDB file
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Key reference
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Title
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Calcium-Controlled conformational choreography in the n-Terminal half of adseverin.
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Authors
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S.Chumnarnsilpa,
R.C.Robinson,
J.M.Grimes,
C.Leyrat.
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Ref.
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Nat Commun, 2015,
6,
8254.
[DOI no: ]
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PubMed id
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Abstract
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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.
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