Domain swapping of a llama VHH domain builds a crystal‐wide β‐sheet structure

FEBS Letters

Tegoni, Mariella¹  Cambillau, Christian¹  Spinelli, Silvia¹  Verrips, Theo²  Frenken, Leon²  Desmyter, Aline¹ 

[1]Architecture et Fonction des Macromolécules Biologiques, UMR-6098, CNRS and Universités d'Aix-Marseille I and II, 31 Chemin Joseph Aiguier, 13402 Marseille Cedex 20, France

[2]Unilever Research Vlaardingen, Olivier van Noortlaan 120, 3133 AT Vlaardingen, The Netherlands

关键词: Crystal structure;    Camelid heavy-chain antibody VH domain;    Immunoglobulin;    Red dye hapten;    Domain swapping;    VHH;    camelid heavy-chain antibody VH domain;    CDR;    complementarity determining region;    FU;    functional unit of domain-swapped dimers;   

DOI  :  10.1016/S0014-5793(04)00304-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Among mammals, camelids have a unique immunological system since they produce functional antibodies devoid of light chains and CH1 domains. To bind antigens, whether they are proteins or haptens, camelids use the single domain VH from their heavy chain (VHH). We report here on such a llama VHH domain (VHH-R9) which was raised against a hapten, the RR6 red dye. This VHH possesses the shortest complementarity determining region 3 (CDR3) among all the known VHH sequences and nevertheless binds RR6 efficiently with a K _d value of 83 nM. However, the crystal structure of VHH-R9 exhibits a striking feature: its CDR3 and its last β-strand (β9) do not follow the immunoglobulin VH domain fold, but instead extend out of the VHH molecular boundary and associate with a symmetry-related molecule. The two monomers thus form a domain-swapped dimer which establishes further contacts with symmetry-related molecules and build a crystal-wide β-sheet structure. The driving force of the dimer formation is probably the strain induced by the short CDR3 together with the cleavage of the first seven residues.

【 授权许可】

Unknown