Crystal structures of two mutant neuraminidase-antibody complexes with amino acid substitutions in the interface.
Crystal structures of two mutant neuraminidase-antibody complexes with amino acid substitutions in the interface.
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DOI：
10.1016/0022-2836(92)90688-g
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发表时间：
1992-09
影响因子：
5.6
通讯作者：
W. R. Tulip;W. R. Tulip;J. Varghese;R. Webster;W. Laver;P. Colman
中科院分区：
文献类型：
--
作者：
W. R. Tulip;W. R. Tulip;J. Varghese;R. Webster;W. Laver;P. Colman
被NC 41单克隆抗体识别的流感病毒N9神经氨酸酶上的位点包含19个氨基酸残基，其与抗体上的17个残基直接接触。该位点中某些神经氨酸酶残基的单序列变化显著降低抗体结合。然而，在该位点内发现了两个突变体，Ile 368突变为Arg，Asn 329突变为Asp，这些突变体与NC 41抗体的结合亲和力仅略有降低。两种结构都表明，一些氨基酸取代可以通过突变位点周围的局部结构重排容纳在抗原-抗体界面内。在Ile 368与Arg突变体复合物中，Arg 368的侧链从其在未复合突变体中的位置移动了2.9个碱基，并且还观察到轻链残基HisL 55的位置相对于野生型复合物移动了1.3个碱基。在另一个突变体中，Asp 329的侧链相对于未复合的突变体围绕C α → Cβ旋转了150°，因此羧酸基团移动到抗原-抗体界面的外围。结果提供了一个基础，了解一些潜在的结构影响体细胞超突变的抗原-抗体结合在这些情况下，在抗体中的突变发生在抗原接触残基，并再次证明了结构背景的重要性，在评估氨基酸取代对蛋白质结构和功能的影响。
The site on influenza virus N9 neuraminidase recognized by NC41 monoclonal antibody comprises 19 amino acid residues that are in direct contact with 17 residues on the antibody. Single sequence changes in some of the neuraminidase residues in the site markedly reduce antibody binding. However, two mutants have been found within the site, Ile368 to Arg and Asn329 to Asp selected by antibodies other than NC41, and these mutants bind NC41 antibody with only slightly reduced affinity.The three-dimensional structures of the two mutant N9-NC41 antibody complexes as derived from the wild-type complex are presented. Both structures show that some amino acid substitutions can be accommodated within an antigen-antibody interface by local structural rearrangements around the mutation site. In the Ile368 to Arg mutant complex, the side-chain of Arg368 is shifted by 2·9 Å from its position in the uncomplexed mutant and a shift of 1·3 Å in the position of the light chain residue HisL55 with respect to the wild-type complex is also observed. In the other mutant, the side-chain of Asp329 appears rotated by 150° aroundCαCβwith respect to the uncomplexed mutant, so that the carboxylate group is moved to the periphery of the antigen-antibody interface. The results provide a basis for understanding some of the potential structural effects of somatic hypermutation on antigen-antibody binding in those cases where the mutation in the antibody occurs at antigen-contacting residues, and demonstrate again the importance of structural context in evaluating the effect of amino acid substitutions on protein structure and function.