Llama heavy-chain V regions consist of at least four distinct subfamilies revealing novel sequence features
Llama heavy-chain V regions consist of at least four distinct subfamilies revealing novel sequence features
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DOI：
10.1016/s0161-5890(00)00081-x
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发表时间：
2000-08-01
影响因子：
3.6
通讯作者：
de Geus, B
中科院分区：
文献类型：
--
作者：
Harmsen, MM;Ruuls, RC;de Geus, B
除了传统的抗体(Abs)外，骆驼还拥有仅由重链组成的Abs。这种重链抗体(VHH)的可变区完全能够与抗原(Ag)结合。早期对47个VHH的分析显示了VHH结构域特有的序列特征。这些包括在传统的VH结构域中参与结构域间相互作用的位置上存在特征氨基酸取代，以及存在一个长的第三互补决定区域(CDR3)，该区域经常受到环间二硫键的限制。在这里，我们描述了一大组(152)喇嘛喇嘛VHH cDNA。根据氨基酸序列的相似性，将这些VHH与其他已发表的骆驼VHH亚家族划分为四个亚家族。到目前为止，独角兽中没有三个亚家族，这是VHH的主要来源。将这些亚家族与传统的VH区进行比较，揭示了VHH的新特征，并表明许多早期被认为是VHH特征的特征实际上是亚科特有的。只在两个VHH亚家族中观察到一个长的CDR3伴随着一个推测的额外的二硫键。此外，我们在传统VH结构域中形成结构域间位点的位置发现了新的VHH特征残基。VHH亚家族在CDR1和CDR2的典范结构、CDR3的平均长度和氨基酸残基的可变性方面也不同于彼此和传统的VH结构域。由于在所有四个亚家族中观察到不同的VHH特征残基，这些亚家族肯定是独立于经典的VH结构域而进化的。(C)2001爱思唯尔科学有限公司。保留所有权利。
In addition to conventional antibodies (Abs), camelids possess Abs consisting of only heavy chains. The variable domain of such a heavy-chain Ab (VHH) is fully capable of antigen (Ag) binding. Earlier analysis of 47 VHHs showed sequence features unique to VHH domains. These include the presence of characteristic amino acid substitutions in positions which, in conventional VH domains are involved in interdomain interactions, and the presence of a long third complementarity-determining region (CDR3) which is frequently constrained by an interloop disulphide bond. Here, we describe a large (152) set of Lama glama VHH cDNAs. Based on amino acid sequence similarity, these and other published camelid VHHs were classified into four subfamilies. Three subfamilies are absent in dromedaries, which have been the primary source of VHHs thus far. Comparison of these subfamilies to conventional VH regions reveals new features characteristic of VHHs and shows that many features earlier regarded as characteristic of VHHs in general are actually subfamily specific. A long CDR3 with a concomitant putative additional disulphide bond is only observed in two VHH subfamilies. Furthermore, we identified new VHH-characteristic residues at positions forming interdomain sites in conventional VH domains. The VHH subfamilies also differ from each other and conventional VH domains in the canonical structure of CDR1 and CDR2, mean CDR3 length, and amino acid residue variability. Since different VHH-characteristic residues are observed in all four subfamilies, these subfamilies must have evolved independently from classical VH domains. (C) 2001 Elsevier Science Ltd. All rights reserved.