Crystal Structure of a Human Single Domain Antibody Dimer Formed through VH-VH Non-Covalent Interactions
Crystal Structure of a Human Single Domain Antibody Dimer Formed through VH-VH Non-Covalent Interactions
复制标题
DOI：
10.1371/journal.pone.0030149
复制
发表时间：
2012-01-12
期刊：
影响因子：
3.7
通讯作者：
Wang, Shuying
中科院分区：
文献类型：
--
作者：
Baral, Toya Nath;Chao, Shi-Yu;Wang, Shuying
来源于人V-H的单域抗体（sabs）被认为是可溶性较低且易于聚集的，这使得很难确定其晶体结构。在这项研究中，我们从合成的人V-H噬菌体展示文库中分离并鉴定了两个抗人表皮生长因子受体-2 （HER2）单克隆抗体Gr3和Gr6。尺寸排除色谱和表面等离子体共振分析表明Gr3是一个单体，而Gr6是一个严格的二聚体。为了了解这种不同的分子行为，我们将Gr6的晶体结构求解到1.6埃的分辨率。晶体结构表明，Gr6的同二聚体组装与免疫球蛋白可变结构域的V-H-V-L异二聚体非常相似，二聚界面以疏水相互作用为主。
Single-domain antibodies (sdAbs) derived from human V-H are considered to be less soluble and prone to aggregate which makes it difficult to determine the crystal structures. In this study, we isolated and characterized two anti-human epidermal growth factor receptor-2 (HER2) sdAbs, Gr3 and Gr6, from a synthetic human V-H phage display library. Size exclusion chromatography and surface plasmon resonance analyses demonstrated that Gr3 is a monomer, but that Gr6 is a strict dimer. To understand this different molecular behavior, we solved the crystal structure of Gr6 to 1.6 angstrom resolution. The crystal structure revealed that the homodimer assembly of Gr6 closely mimics the V-H-V-L heterodimer of immunoglobulin variable domains and the dimerization interface is dominated by hydrophobic interactions.