Structural determinants in the sequences of immunoglobulin variable domain
Structural determinants in the sequences of immunoglobulin variable domain
复制标题
DOI：
10.1006/jmbi.1998.1653
复制
发表时间：
1998-05-01
影响因子：
5.6
通讯作者：
Kister, A
中科院分区：
文献类型：
--
作者：
Chothia, C;Gelfand, I;Kister, A
为了确定免疫球蛋白可变结构域的序列和结构之间的一般关系，我们对免疫球蛋白的原子结构、大约5300个不同的表达序列和人类种系基因片段进行了分析。可变结构域是由两个β -薄片组成的，它们面对面地排列在一起，并且在链间旋转。对不同已知结构的比较表明，它们的核心有76个残基，在所有结构中具有相同的主链构象。这个共同的核心包含了几乎所有的β -片结构和三个链间匝。构象不同的区域是三个高变区，三个其他的链间弯和一些相邻的残基。对5300个目前已知的可变结构域表达序列进行了检查，以确定76个位点上的残基。忽略由于功能原因而发生的位点保守，在几乎所有序列中有8个位点具有相同的残基；12种是有一小群非常相似的残基，52种是残基的化学性质非常保守，但它们的体积却不守恒。残基在核心中每个位点的作用是通过检查其可接近的表面积、接触、填料和埋藏的侧链氢键来确定的。最强烈保守的位点在β -片之间界面的中心形成了结构域的“深层”结构。它包括8个不变位点和11个有一个非常相似残基的位点。在深层结构周围有埋藏的疏水残基，在不同的可变结构域中，它们的体积差异很大。这些体积上的差异是由共同核外区域的构象变化所调节的。在表面上，几乎所有不参与功能构象或转动构象的残基都强烈保留亲水性或中性残基。讨论了这些结果对蛋白质序列和结构之间的一般关系的意义。(C) 1998学术出版社有限公司
To determine the general relation between the sequence and structure of variable domains of immunoglobulins we have carried out an analysis of their atomic structures, some 5300 different expressed sequences and the human germline gene segments. Variable domains are formed by two beta-sheets, packed face to face, and the inter-strand turns. Comparison of the different known structures shows that they have a core of 76 residues which has the same main-chain conformation in all structures. This common core contains almost all of the beta-sheet structure and three interstrand turns. The regions that differ in conformation are the three hypervariable regions, three other inter-strand turns and a few adjacent residues.The 5300 expressed sequences currently known for variable domains were examined to determine the residues that occur at the 76 sites. Ignoring site conservations that occur for functional reasons, there are eight sites that have the same residue in almost all sequences; 12 that have one of a small group of very similar residues, and 52 where the chemical character of the residues is strongly conserved but not their volume.The role of residues at each site in the core was determined from the examination of their accessible surface areas, contacts, packing and buried side-chain hydrogen bonds. The most strongly conserved sites form the "deep" structure of the domain at the centre of the interface between the beta-sheets. It includes eight invariant sites and 11 sites that have one of a set of very similar residues. Around the deep structure there are buried hydrophobic residues that, in different variable domains, can differ greatly in volume. These differences in volume are accommodated by conformational changes in turn regions that are outside the common core. On the surface nearly all residues not involved in function or turn conformations strongly conserve hydrophilic or neutral residues.The implications of these results for the general relations between the sequence and structure of proteins are discussed. (C) 1998 Academic Press Limited.