In silico analysis of Glanzmann variants of Calf-1 domain of α_IIbβ₃ integrin revealed dynamic allosteric effect.

ABSTRACT: Integrin α_IIbβ₃ mediates platelet aggregation and thrombus formation. In a rare hereditary bleeding disorder, Glanzmann thrombasthenia (GT), α_IIbβ₃ expression / function are impaired. The impact of deleterious missense mutations on the complex structure remains unclear. Long independent molecular dynamics (MD) simulations were performed for 7 GT variants and reference structure of the Calf-1 domain of α_IIb. Simulations were analysed using a structural alphabet to describe local protein conformations. Common and flexible regions as well as deformable zones were observed in all the structures. The most flexible region of Calf-1 (with highest B-factor) is rather a rigid region encompassed into two deformable zones. Each mutated structure

SUBMITTER: Goguet M 

PROVIDER: S-EPMC5556033 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature