PDBsum entry 5a1m

Actin-binding protein

PDB id: 5a1m

Contents

Protein chain

104 a.a.

Metals

_CA

Waters ×164

PDB id:

5a1m

Name:

Actin-binding protein

Title:

Crystal structure of calcium-bound human adseverin domain a3

Structure:

Adseverin. Chain: a. Fragment: domain a3, residues 247-350. Synonym: scinderin. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 469008. Expression_system_variant: rosetta.

Resolution:

1.81Å R-factor: 0.182 R-free: 0.189

Authors:

S.Chumnarnsilpa,R.C.Robinson,J.M.Grimes,C.Leyrat

Key ref:

S.Chumnarnsilpa et al. (2015). Calcium-controlled conformational choreography in the N-terminal half of adseverin. Nat Commun, 6, 8254. PubMed id: 26365202 DOI: 10.1038/ncomms9254

Date:

01-May-15 Release date: 16-Sep-15

Protein chain

Q9Y6U3  (ADSV_HUMAN) -  Scinderin from Homo sapiens

Seq: 715 a.a.

Struc: 104 a.a.

DOI no: 10.1038/ncomms9254

Nat Commun 6:8254 (2015)

PubMed id: 26365202

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

S.Chumnarnsilpa, R.C.Robinson, J.M.Grimes, C.Leyrat.

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.