Abstract

Nanobodies are a class of antigen-binding protein derived from heavy-chain antibodies in camels, llamas and alpacas. They achieve high affinity binding specificities equivalent to antibodies; despite comprising only a single 15 kDa variable domain. Their restricted size greatly reduces the possible sequence space available for encoding specificity, making the question underpinning the sequence-specificity relationship more tractable. In this talk I present sequence and structural analysis of the largest set of nanobody:antigen co-crystal structures compiled to date, which has revealed surprising findings relating to the conservation of nanobody framework regions, the composition of nanobody sequence-variable loops and the distribution of specificity-determining residues.