IMMUNOGLOBULIN VH CLAN AND FAMILY IDENTITY PREDICTS VARIABLE DOMAIN-STRUCTURE AND MAY INFLUENCE ANTIGEN-BINDING
IMMUNOGLOBULIN VH CLAN AND FAMILY IDENTITY PREDICTS VARIABLE DOMAIN-STRUCTURE AND MAY INFLUENCE ANTIGEN-BINDING
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DOI：
10.1002/j.1460-2075.1992.tb05092.x
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发表时间：
1992-02-01
期刊：
影响因子：
11.4
通讯作者：
SCHROEDER, HW
中科院分区：
文献类型：
--
作者：
KIRKHAM, PM;MORTARI, F;SCHROEDER, HW
哺乳动物免疫球蛋白VH家族可以根据三个框架(FR)区间中的两个序列的保守性分为三个不同的家族。通过置换/沉默位点替换分析、分子模拟和已知免疫球蛋白晶体结构的数学评估，我们证明这种保守性反映了蛋白质序列和结构的保留。每个家族都含有一个特征的FR 1区间，该区间暴露在溶剂中，在结构上与抗原结合部位分离。一个氏族内的家族都有自己独特的FR3区间，能够影响抗原结合位点的构象或直接与抗原相互作用。我们的结果为解决V(HN)家族在免疫反应中的不同使用的理论提供了结构背景。
Mammalian immunoglobulin VH families can be grouped into three distinct clans based upon sequence conservation in two of the three framework (FR) intervals. Through replacement/silent site substitution analysis, molecular modeling and mathematical evaluation of known immunoglobulin crystal structures, we demonstrate that this conservation reflects preservation of protein sequence and structure. Each clan contains a characteristic FR 1 interval that is solvent-exposed and structurally separated from the antigen binding site. Families within a clan contain their own unique FR 3 interval that is capable of either influencing the conformation of the antigen binding site or interacting directly with antigen. Our results provide a structural context for theories that address differential use Of V(HN) families in the immune response.