In silico analysis of structural modifications in and around the integrin αIIb genu caused by ITGA2B variants in human platelets with emphasis on Glanzmann thrombasthenia.

ABSTRACT:

Background

Studies on the inherited bleeding disorder, Glanzmann thrombasthenia (GT), have helped define the role of the αIIbβ3 integrin in platelet aggregation. Stable bent αIIbβ3 undergoes conformation changes on activation allowing fibrinogen binding and its taking an extended form. The αIIb genu assures the fulcrum of the bent state. Our goal was to determine how structural changes induced by missense mutations in the αIIb genu define GT phenotype.

Methods

Sanger sequencing of ITGA2B and ITGB3 in the index case followed by in silico modeling of all known GT-causing missense mutations extending from the lower part of the β-propeller, and through the thigh and upper calf-1 domains.

Results

A homozygous c.1772A>C transversion in exon 18 of ITGA2B coding for a p.Asp59

SUBMITTER: Pillois X 

PROVIDER: S-EPMC5902390 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature