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.
Copyright © 2014 Elsevier Inc. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Amino Acid Substitution
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CD18 Antigens / chemistry*
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CD18 Antigens / genetics
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CD18 Antigens / metabolism
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Cell Adhesion
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Gene Expression
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HEK293 Cells
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Humans
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Leukocyte-Adhesion Deficiency Syndrome / genetics
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Leukocyte-Adhesion Deficiency Syndrome / pathology
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Leukocytes / metabolism
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Leukocytes / pathology
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Models, Molecular
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Molecular Sequence Data
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Mutation, Missense*
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Plasmids / chemistry
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Plasmids / metabolism
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Protein Structure, Secondary
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Protein Structure, Tertiary
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Protein Subunits / chemistry*
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Protein Subunits / genetics
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Protein Subunits / metabolism
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Recombinant Proteins / chemistry
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Sequence Alignment
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Transfection
Substances
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CD18 Antigens
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Protein Subunits
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Recombinant Proteins