Structural origins of misfolding propensity in the platelet adhesive von Willebrand factor A1 domain.

ABSTRACT: The von Willebrand factor (VWF) A1 and A3 domains are structurally isomorphic yet exhibit distinct mechanisms of unfolding. The A1 domain, responsible for platelet adhesion to VWF in hemostasis, unfolds through a molten globule intermediate in an apparent three-state mechanism, while A3 unfolds by a classical two-state mechanism. Inspection of the sequences or structures alone does not elucidate the source of this thermodynamic conundrum; however, the three-state character of the A1 domain suggests that it has more than one cooperative substructure yielding two separate unfolding transitions not present in A3. We investigate the extent to which structural elements contributing to intermediate conformations can be identified using a residue-specific implementation of the structure-energy-eq

SUBMITTER: Zimmermann MT 

PROVIDER: S-EPMC4621621 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature