5a1m | pdb_00005a1m
Crystal structure of calcium-bound human adseverin domain A3
Structural highlights
Function[ADSV_HUMAN] Ca(2+)-dependent actin filament-severing protein that is presumed to have a regulatory function in exocytosis by affecting the organization of the microfilament network underneath the plasma membrane. In vitro, also has barbed end capping and nucleating activities in the presence of Ca(2+). Regulates chondrocyte proliferation and differentiation. MAP kinases p38 and ERK1/2 mediate the adseverin-induced accelerated differentiation of non-hypertrophic chondrocytes (By similarity). Publication Abstract from PubMedAdseverin 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. Calcium-controlled conformational choreography in the N-terminal half of adseverin.,Chumnarnsilpa S, Robinson RC, Grimes JM, Leyrat C Nat Commun. 2015 Sep 14;6:8254. doi: 10.1038/ncomms9254. PMID:26365202[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||||
