5A1K

Crystal structure of calcium-free human adseverin domains A1-A3

Summary for 5A1K

• Entry DOI: 10.2210/pdb5a1k/pdb
• Related: 5A1M
• Descriptor: ADSEVERIN (2 entities in total)
• Functional Keywords: actin-binding protein, actin
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Cytoplasm, cytoskeleton: Q9Y6U3
• Total number of polymer chains: 2
• Total formula weight: 77599.65

Authors

Chumnarnsilpa, S.,Robinson, R.C.,Grimes, J.M.,Leyrat, C. (deposition date: 2015-04-30, release date: 2015-09-16, Last modification date: 2024-01-10)

Primary citation

Chumnarnsilpa, S.,Robinson, R.C.,Grimes, J.M.,Leyrat, C.
Calcium-Controlled Conformational Choreography in the N-Terminal Half of Adseverin.
Nat.Commun., 6:8254-, 2015

PubMed 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.

PubMed: 26365202
DOI: 10.1038/NCOMMS9254

Experimental method

X-RAY DIFFRACTION (2.9 Å)