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

Siyu Guan; Suet Mien Tan; Yan Li; Jaume Torres; Gulbu Uzel; Liming Xiang; S. K.Alex Law

doi:10.1016/j.bcmd.2014.11.005

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

Siyu Guan, Suet Mien Tan, Yan Li, Jaume Torres, Gulbu Uzel, Liming Xiang, S. K.Alex Law^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

11 Citations (Scopus)

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.

Original language	English
Pages (from-to)	177-182
Number of pages	6
Journal	Blood Cells, Molecules, and Diseases
Volume	54
Issue number	2
DOIs	https://doi.org/10.1016/j.bcmd.2014.11.005
Publication status	Published - 2015
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2014 Elsevier Inc.

ASJC Scopus Subject Areas

Molecular Medicine
Molecular Biology
Hematology
Cell Biology

Keywords

Cell adhesion
Expression
LAD-1
Missense mutation
β2 (CD18) integrin

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10.1016/j.bcmd.2014.11.005

Cite this

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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.",

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author = "Siyu Guan and Tan, {Suet Mien} and Yan Li and Jaume Torres and Gulbu Uzel and Liming Xiang and Law, {S. K.Alex}",

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year = "2015",

doi = "10.1016/j.bcmd.2014.11.005",

language = "English",

volume = "54",

pages = "177--182",

journal = "Blood Cells, Molecules, and Diseases",

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T1 - Characterization of single amino acid substitutions in the β2 integrin subunit of patients with leukocyte adhesion deficiency (LAD)-1

AU - Guan, Siyu

AU - Tan, Suet Mien

AU - Li, Yan

AU - Torres, Jaume

AU - Uzel, Gulbu

AU - Xiang, Liming

AU - Law, S. K.Alex

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

KW - Cell adhesion

KW - Expression

KW - LAD-1

KW - Missense mutation

KW - β2 (CD18) integrin

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

Abstract

Bibliographical note

ASJC Scopus Subject Areas

Keywords

Access to Document

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