FRAMEWORK RESIDUE-71 IS A MAJOR DETERMINANT OF THE POSITION AND CONFORMATION OF THE 2ND HYPERVARIABLE REGION IN THE VH DOMAINS OF IMMUNOGLOBULINS
FRAMEWORK RESIDUE-71 IS A MAJOR DETERMINANT OF THE POSITION AND CONFORMATION OF THE 2ND HYPERVARIABLE REGION IN THE VH DOMAINS OF IMMUNOGLOBULINS
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DOI：
10.1016/s0022-2836(05)80102-0
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发表时间：
1990-09-05
影响因子：
5.6
通讯作者：
LESK, AM
中科院分区：
文献类型：
--
作者：
TRAMONTANO, A;CHOTHIA, C;LESK, AM
已知结构的免疫球蛋白的分析揭示了VH结构域（H2）的第二高变区的位置和主链构象的系统差异。我们表明，H2的位置的主要决定因素是在网站71，一个网站，是在保守的自由基的VH结构域的残基的大小。可能对于约三分之二的已知VH序列，该位点处残基的大小也是H2构象的主要决定因素。这种效应可以超越序列的倾向性，如在J539的H2环的情况下，这是与短发夹环的序列和构象相关的规则的例外。了解71位残基与H2的位置和构象之间的关系可应用于免疫球蛋白抗原结合位点的预测和工程化。
Analysis of the immunglobulins of known structure reveals systematic differences in the position and main-chain conformation of the second hypervariable region of the VH domain (H2). We show that the major determinant of the position of H2 is the size of the residue at site 71, a site that is in the conserved freamework of the VH domain. It is likely that for about two thirds of the known VH sequences the size of the residue at this site is also a major determinant of the conformation of H2. This effect can override the predisposition of the sequence, as in the case of H2 loop of J539, which is an exception to the rules relating sequence and conformation of short hairpin loops. Understanding the relationship between the residue at position 71 and the position and conformation of H2 has applications to the prediction and engineering of antigen-binding sites of immunoglobulins.