Characterization of single amino acid substitutions in the β2 integrin subunit of patients with leukocyte adhesion deficiency (LAD)-1

Blood Cells Mol Dis. 2015 Feb;54(2):177-82. doi: 10.1016/j.bcmd.2014.11.005. Epub 2014 Nov 28.

Abstract

Leukocyte adhesion deficiency 1 (LAD-1) is caused by defects in the β2 integrin subunit. We studied 18 missense mutations, 14 of which fail to support the surface expression of the β2 integrins. Integrins with the β2-G150D mutation fail to bind ligands, possibly due to the failure of the α1 segment of the βI domain to assume an α-helical structure. Integrins with the β2-G716A mutation are not maintained in their resting states, and the patient has the severe phenotype of LAD-1. The β2-S453N and β2-P648L mutants support the expression of integrins and adhesion functions. They should be re-classified as polymorphic variants.

Keywords: Cell adhesion; Expression; LAD-1; Missense mutation; β2 (CD18) integrin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution
  • CD18 Antigens / chemistry*
  • CD18 Antigens / genetics
  • CD18 Antigens / metabolism
  • Cell Adhesion
  • Gene Expression
  • HEK293 Cells
  • Humans
  • Leukocyte-Adhesion Deficiency Syndrome / genetics
  • Leukocyte-Adhesion Deficiency Syndrome / pathology
  • Leukocytes / metabolism
  • Leukocytes / pathology
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation, Missense*
  • Plasmids / chemistry
  • Plasmids / metabolism
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Protein Subunits / chemistry*
  • Protein Subunits / genetics
  • Protein Subunits / metabolism
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Sequence Alignment
  • Transfection

Substances

  • CD18 Antigens
  • Protein Subunits
  • Recombinant Proteins