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

Variable heavy domains derived from the heavy-chain-only antibodies found in camelids (V_HH domains) are known for their thermal stability. Here, the structure of A9, an anti-cholera toxin V_HH 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 β-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.