title: A novel amino acid substitution of integrin αIIb in Glanzmann thrombasthenia confirms that the N-terminal region of the receptor plays a role in maintaining β-propeller structure.
abstract: Mutation screening in Glanzmann thrombasthenia (GT) is now advanced. Despite the large number of genetic defects reported in the ITGA2B gene, few affect the structure of the N-terminal domain of the αIIb subunit. We now report a Catalan family where type I GT is given by compound heterozygosity within ITGA2B with a Gly13Val substitution in αIIb associated with a 13 bp deletion involving the splice site of exon 15. Molecular modelling confirmed that the Gly13Val mutation interfered with the structure of the αIIb β-propeller and confirms that a fold-back of the N-terminus to interact with residues deep within the propeller is necessary for the normal intracellular processing of the maturing αIIbβ3 integrin.
authors.forename: Xavier
authors.initials: X
authors.lastname: Pillois
authors.forename: Mathieu
authors.initials: M
authors.lastname: Fiore
authors.forename: Roland
authors.initials: R
authors.lastname: Heilig
authors.forename: Marta
authors.initials: M
authors.lastname: Pico
authors.forename: Alan T
authors.initials: AT
authors.lastname: Nurden
mesh_terms: D019943:Amino Acid Substitution; D001483:Base Sequence; D006801:Humans; D039661:Integrin beta3 / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D040201:Platelet Membrane Glycoprotein IIb / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D013915:Thrombasthenia / Q000235:genetics*
chemical_list: D039661:Integrin beta3; D040201:Platelet Membrane Glycoprotein IIb