白细胞黏附缺陷症（LAD）-1患者β2整合素亚基中单个氨基酸替代的特征分析

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

作者信息

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

机构信息

School of Biological Sciences, Nanyang Technological University, Singapore.

Laboratory of Infectious Disease, National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, MD, USA.

出版信息

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

DOI:10.1016/j.bcmd.2014.11.005

PMID:25514840

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.

摘要

白细胞黏附缺陷1型（LAD-1）是由β2整合素亚基缺陷引起的。我们研究了18个错义突变，其中14个不能支持β2整合素的表面表达。具有β2-G150D突变的整合素无法结合配体，这可能是由于βI结构域的α1片段未能形成α螺旋结构所致。具有β2-G716A突变的整合素不能维持其静止状态，该患者具有LAD-1的严重表型。β2-S453N和β2-P648L突变体支持整合素的表达和黏附功能。它们应重新分类为多态性变体。