Maturation of shark single-domain (IgNAR) antibodies: Evidence for induced-fit binding
Maturation of shark single-domain (IgNAR) antibodies: Evidence for induced-fit binding
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DOI：
10.1016/j.jmb.2006.12.045
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发表时间：
2007-03-23
影响因子：
5.6
通讯作者：
Wilson, Ian A.
中科院分区：
文献类型：
--
作者：
Stanfield, Robyn L.;Dooley, Helen;Wilson, Ian A.
鲨鱼表达一种称为IgNAR的不寻常的重链同种型，其可变区作为独立的可溶性结构域结合抗原。为了进一步探测IgNAR反应的亲和力成熟，我们在结构上表征了II型可变（V）区的种系和体细胞成熟版本，无论是在存在还是不存在其抗原，鸡蛋清溶菌酶的情况下。尽管二硫键连接互补决定区（CDR）1和3，生殖系和体细胞成熟的V区显示显着的结构变化，这些CDR与抗原形成复合物后。IgNAR V区中的体细胞突变用于增加与抗原的接触次数，如亲和力增加10倍所反映的，并且这些突变之一似乎稳定了CDR 3区。此外，HV 4环中的残基在抗体-抗原相互作用中起重要作用，这与该非CDR环中的高体细胞突变率一致。(c)2007爱思唯尔有限公司保留所有权利。
Sharks express an unusual heavy-chain isotype called IgNAR, whose variable regions bind antigen as independent soluble domains. To further probe affinity maturation of the IgNAR response, we structurally characterized the germline and somatically matured versions of a type II variable (V) region, both in the presence and absence of its antigen, hen egg-white lysozyme. Despite a disulfide bond linking complementarity determining regions (CDRs) 1 and 3, both germline and somatically matured V regions displayed significant structural changes in these CDRs upon complex formation with antigen. Somatic mutations in the IgNAR V region serve to increase the number of contacts with antigen, as reflected by a tenfold increase in affinity and one of these mutations appears to stabilize the CDR3 region. In addition, a residue in the HV4 loop plays an important role in antibody-antigen interaction, consistent with the high rate of somatic mutations in this non-CDR loop. (c) 2007 Elsevier Ltd. All rights reserved.