Molecular dynamics analysis of a novel β3 Pro189Ser mutation in a patient with glanzmann thrombasthenia differentially affecting αIIbβ3 and αvβ3 expression.

ABSTRACT: Mutations in ITGA2B and ITGB3 cause Glanzmann thrombasthenia, an inherited bleeding disorder in which platelets fail to aggregate when stimulated. Whereas an absence of expression or qualitative defects of αIIbβ3 mainly affect platelets and megakaryocytes, αvβ3 has a widespread tissue distribution. Little is known of how amino acid substitutions of β3 comparatively affect the expression and structure of both integrins. We now report computer modelling including molecular dynamics simulations of extracellular head domains of αIIbβ3 and αvβ3 to determine the role of a novel β3 Pro189Ser (P163S in the mature protein) substitution that abrogates αIIbβ3 expression in platelets while allowing synthesis of αvβ3. Transfection of wild-type and mutated integrins in CHO cells confirmed that only αvβ3

SUBMITTER: Laguerre M 

PROVIDER: S-EPMC3827234 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature