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The impact of exchanging the light and heavy chains on the structures of bovine ultralong antibodies.

Authors :
Clarke JD
Douangamath A
Mikolajek H
Bonnet-Di Placido M
Ren J
Fry EE
Stuart DI
Hammond JA
Owens RJ
Source :
Acta crystallographica. Section F, Structural biology communications [Acta Crystallogr F Struct Biol Commun] 2024 Jul 01; Vol. 80 (Pt 7), pp. 154-163. Date of Electronic Publication: 2024 Jul 01.
Publication Year :
2024

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.<br /> (open access.)

Details

Language :
English
ISSN :
2053-230X
Volume :
80
Issue :
Pt 7
Database :
MEDLINE
Journal :
Acta crystallographica. Section F, Structural biology communications
Publication Type :
Academic Journal
Accession number :
38958188
Full Text :
https://doi.org/10.1107/S2053230X2400606X