Structural Basis of Epitope Recognition by Heavy-Chain Camelid Antibodies.

Uroš Zavrtanik, Junoš Lukan, Remy Loris, Jurij Lah, San Hadzi

Onderzoeksoutput: Articlepeer review

75 Citaten (Scopus)

Samenvatting

Truncated versions of heavy-chain antibodies (HCAbs) from camelids, also termed nanobodies, comprise only one-tenth the mass of conventional antibodies, yet retain similar, high binding affinities for the antigens. Here we analyze a large data set of nanobody-antigen crystal structures and investigate how nanobody-antigen recognition compares to the one by conventional antibodies. We find that nanobody paratopes are enriched in aromatic residues just like conventional antibodies, but additionally, they also bear a more hydrophobic character. Most striking differences were observed in the characteristics of the antigen's epitope. Unlike conventional antibodies, nanobodies bind to more rigid, concave, conserved and structured epitopes enriched with aromatic residues. Nanobodies establish fewer interactions with the antigens compared to conventional antibodies, and we speculate that high binding affinities are achieved due to less unfavorable conformational and more favorable solvation entropy contributions. We observed that interactions with antigen are mediated not only by three CDR loops but also by numerous residues from the nanobody framework. These residues are not distributed uniformly; rather, they are concentrated into four structurally distinct regions and mediate mostly charged interactions. Our findings suggest that in some respects nanobody-antigen interactions are more similar to the general protein-protein interactions rather than antibody-antigen interactions.
Originele taal-2English
Pagina's (van-tot)4369-4386
Aantal pagina's18
TijdschriftJ Mol Biol
Volume430
Nummer van het tijdschrift21
DOI's
StatusPublished - 19 okt 2018

Vingerafdruk

Duik in de onderzoeksthema's van 'Structural Basis of Epitope Recognition by Heavy-Chain Camelid Antibodies.'. Samen vormen ze een unieke vingerafdruk.

Citeer dit