Structural Diversity of Ultralong CDRH3s in Seven Bovine Antibody Heavy Chains

Dong, Jinhui; Finn, Jessica A.; Larsen, Peter A.; Smith, Timothy P. L.; Crowe, Jr., James E.

doi:10.3389/fimmu.2019.00558

Structural Diversity of Ultralong CDRH3s in Seven Bovine Antibody Heavy Chains

Journal Article · Fri Mar 22 00:00:00 EDT 2019 · Frontiers in Immunology

DOI:https://doi.org/10.3389/fimmu.2019.00558· OSTI ID:1503947

Dong, Jinhui; Finn, Jessica A.; Larsen, Peter A.; Smith, Timothy P. L.; Crowe, Jr., James E.

Antigen recognition by mammalian antibodies represents the most diverse setting for protein-protein interactions, because antibody variable regions contain exceptionally diverse variable gene repertoires of DNA sequences containing combinatorial, non-templated junctional mutational diversity. Some animals use additional strategies to achieve structural complexity in the antibody combining site, and one of the most interesting of these is the formation of ultralong heavy chain complementarity determining region 3 loops in cattle. Repertoire sequencing studies of bovine antibody heavy chain variable sequences revealed that bovine antibodies can contain heavy chain complementarity determining region 3 (CDRH3) loops with 60 or more amino acids, with complex structures stabilized by multiple disulfide bonds. It is clear that bovine antibodies can achieve long, peculiarly structured CDR3s, but the range of diversity and complexity of those structures is poorly understood. We determined the atomic resolution structure of seven ultralong bovine CDRH3 loops. The studies, combined with five previous structures, reveal a large diversity of cysteine pairing variations, and highly diverse globular domains.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: Michigan Economic Development Corporation and the Michigan Technology Tri-Corridor; USDOE Office of Science (SC)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1503947

Alternate ID(s):: OSTI ID: 1545853

Journal Information:: Frontiers in Immunology, Journal Name: Frontiers in Immunology Vol. 10; ISSN 1664-3224

Publisher:: Frontiers Research FoundationCopyright Statement

Country of Publication:: Switzerland

Language:: English

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59 BASIC BIOLOGICAL SCIENCES
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lymphocytes
monoclonal antibody
ultralong CDRH3

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