Structure of a low-melting-temperature anti-cholera toxin: llama VHH domain

Variable heavy domains derived from the heavy-chain-only antibodies found in camelids (VHH domains) are known for their thermal stability. Here, the structure of A9, an anti-cholera toxin VHH domain (K-d = 77 +/- 5 nM) that has an unusually low melting temperature of 319.9 +/- 1.6 K, is reported. The CDR3 residues of A9 form a beta-hairpin that is directed away from the former V-H-V-L interfacial surface, exposing hydrophobic residues to the solvent. A DALI structural similarity search showed that this CDR3 conformation is uncommon.