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Cambridge Biosciences BBSRC DTP


Congratulations to Laura Mitchell, 2014 cohort PhD student in the BBSRC DTP Programme, for publishing the paper Analysis of nanobody paratopes reveals greater diversity than classical antibodies’ in Protein Engineering, Design and Selection.


Nanobodies (Nbs) are a class of antigen-binding protein derived from camelid immune systems, which achieve equivalent binding affinities and specificities to classical antibodies (Abs) despite being comprised of only a single variable domain. Here, we use a data set of 156 unique Nb:antigen complex structures to characterize Nb–antigen binding and draw comparison to a set of 156 unique Ab:antigen structures. We analyse residue composition and interactions at the antigen interface, together with structural features of the paratopes of both data sets. Our analysis finds that the set of Nb structures displays much greater paratope diversity, in terms of the structural segments involved in the paratope, the residues used at these positions to contact the antigen and furthermore the type of contacts made with the antigen. Our findings suggest a different relationship between contact propensity and sequence variability from that observed for Ab VH domains. The distinction between sequence positions that control interaction specificity and those that form the domain scaffold is much less clear-cut for Nbs, and furthermore H3 loop positions play a much more dominant role in determining interaction specificity.

To read the full publication, please click here.

Laura’s PhD research aims to understand and engineer specificity in nanobody-antigen interactions, using sequence and structure based bioinformatics. Laura is also working on an OpenPlant funded project to develop cell-free virus-sensing circuits for application in low-cost agricultural diagnostics.