Summary
The solubilization tetrad, which consists of residues 42, 49, 50, and 52 (Kabat numbering), allows camelid VHH nanobodies to remain soluble in the absence of a light chain (1). Residues 49 and 50 can be back-mutated to human residues but residues 42 and 52 cannot.
See also
1.
Rossotti MA, Bélanger K, Henry KA, Tanha J. Immunogenicity and humanization of single‐domain antibodies. The FEBS Journal. 2021;289(14):4304–27. Available from: https://doi.org/10.1111/febs.15809