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

Platelets. 2013;24(1):77-80. doi: 10.3109/09537104.2012.665278. Epub 2012 Mar 6.

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.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Base Sequence
  • Humans
  • Integrin beta3 / genetics
  • Integrin beta3 / metabolism
  • Mutation
  • Platelet Membrane Glycoprotein IIb / chemistry*
  • Platelet Membrane Glycoprotein IIb / genetics*
  • Platelet Membrane Glycoprotein IIb / metabolism
  • Protein Conformation
  • Protein Interaction Domains and Motifs*
  • Thrombasthenia / genetics*

Substances

  • Integrin beta3
  • Platelet Membrane Glycoprotein IIb