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