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- Title
Domain swapping of a llama VHH domain builds a crystal-wide β-sheet structure
- Authors
Spinelli, Silvia; Desmyter, Aline; Frenken, Leon; Verrips, Theo; Tegoni, Mariella; Cambillau, Christian
- Abstract
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 Kd 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.
- Subjects
IMMUNOGLOBULINS; IMMUNE system; ANTIGENS; MOLECULES
- Publication
FEBS Letters, 2004, Vol 564, Issue 1/2, p35
- ISSN
0014-5793
- Publication type
Article
- DOI
10.1016/S0014-5793(04)00304-7