The impact of exchanging the light and heavy chains on the structures of bovine ultralong antibodies.
Clarke, J.D., Douangamath, A., Mikolajek, H., Bonnet-Di Placido, M., Ren, J., Fry, E.E., Stuart, D.I., Hammond, J.A., Owens, R.J.(2024) Acta Crystallogr F Struct Biol Commun 80: 154-163
- PubMed: 38958188 
- DOI: https://doi.org/10.1107/S2053230X2400606X
- Primary Citation of Related Structures:  
8BS8 - PubMed Abstract: 
The third complementary-determining regions of the heavy-chain (CDR3H) variable regions (VH) of some cattle antibodies are highly extended, consisting of 48 or more residues. These `ultralong' CDR3Hs form β-ribbon stalks that protrude from the surface of the antibody with a disulfide cross-linked knob region at their apex that dominates antigen interactions over the other CDR loops. The structure of the Fab fragment of a naturally paired bovine ultralong antibody (D08), identified by single B-cell sequencing, has been determined to 1.6 Å resolution. By swapping the D08 native light chain with that of an unrelated antigen-unknown ultralong antibody, it is shown that interactions between the CDR3s of the variable domains potentially affect the fine positioning of the ultralong CDR3H; however, comparison with other crystallographic structures shows that crystalline packing is also a major contributor. It is concluded that, on balance, the exact positioning of ultralong CDR3H loops is most likely to be due to the constraints of crystal packing.
Organizational Affiliation: 
The Division of Structural Biology, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, United Kingdom.