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

• Published in: Platelets (Edinburgh) 2013-01, Vol.24 (1), p.77-80
• Main Authors: Pillois, Xavier, Fiore, Mathieu, Heilig, Roland, Pico, Marta, Nurden, Alan T.
• Format: Article
• Language: English
• Subjects: Amino Acid Substitution; Base Sequence; Biochemistry, Molecular Biology; Genetics; Glanzmann thrombasthenia; Human genetics; Humans; Integrin beta3 - genetics; Integrin beta3 - metabolism; ITGA2B; Life Sciences; Molecular biology; Mutation; mutation analysis; Platelet Membrane Glycoprotein IIb - chemistry; Platelet Membrane Glycoprotein IIb - genetics; Platelet Membrane Glycoprotein IIb - metabolism; Protein Conformation; Protein Interaction Domains and Motifs; Thrombasthenia - genetics; αIIbβ3
• ISSN: 0953-7104; 1369-1635
• DOI: 10.3109/09537104.2012.665278

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.