title: Characterization of single amino acid substitutions in the β2 integrin subunit of patients with leukocyte adhesion deficiency (LAD)-1.
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.
authors.affiliation: School of Biological Sciences, Nanyang Technological University, Singapore.
authors.forename: Siyu
authors.initials: S
authors.lastname: Guan
authors.affiliation: School of Biological Sciences, Nanyang Technological University, Singapore.
authors.forename: Suet-Mien
authors.initials: SM
authors.lastname: Tan
authors.affiliation: School of Biological Sciences, Nanyang Technological University, Singapore.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: School of Biological Sciences, Nanyang Technological University, Singapore.
authors.forename: Jaume
authors.initials: J
authors.lastname: Torres
authors.affiliation: Laboratory of Infectious Disease, National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, MD, USA.
authors.forename: Gulbu
authors.initials: G
authors.lastname: Uzel
authors.affiliation: School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore.
authors.forename: Liming
authors.initials: L
authors.lastname: Xiang
authors.affiliation: School of Biological Sciences, Nanyang Technological University, Singapore. Electronic address: alaw@ntu.edu.sg.
authors.forename: S K Alex
authors.initials: SK
authors.lastname: Law
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D018821:CD18 Antigens / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion; D015870:Gene Expression; D057809:HEK293 Cells; D006801:Humans; D018370:Leukocyte-Adhesion Deficiency Syndrome / Q000235:genetics / Q000473:pathology; D007962:Leukocytes / Q000378:metabolism / Q000473:pathology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D014162:Transfection
chemical_list: D018821:CD18 Antigens; D021122:Protein Subunits; D011994:Recombinant Proteins
keywords: Cell adhesion; Expression; LAD-1; Missense mutation; β2 (CD18) integrin