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Title: Structural Diversity of Ultralong CDRH3s in Seven Bovine Antibody Heavy Chains

Abstract

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.

Authors:
; ; ; ;
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
USDOE Office of Science (SC); Michigan Economic Development Corporation and the Michigan Technology Tri-Corridor
OSTI Identifier:
1503947
Alternate Identifier(s):
OSTI ID: 1545853
Grant/Contract Number:  
AC02-06CH11357; 085P1000817
Resource Type:
Published Article
Journal Name:
Frontiers in Immunology
Additional Journal Information:
Journal Name: Frontiers in Immunology Journal Volume: 10; Journal ID: ISSN 1664-3224
Publisher:
Frontiers Research Foundation
Country of Publication:
Switzerland
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; lymphocytes; monoclonal antibody; antigen-antibody recognition; Bos taurus; ultralong CDRH3; crystal structure; disulfide

Citation Formats

Dong, Jinhui, Finn, Jessica A., Larsen, Peter A., Smith, Timothy P. L., and Crowe, Jr., James E. Structural Diversity of Ultralong CDRH3s in Seven Bovine Antibody Heavy Chains. Switzerland: N. p., 2019. Web. doi:10.3389/fimmu.2019.00558.
Dong, Jinhui, Finn, Jessica A., Larsen, Peter A., Smith, Timothy P. L., & Crowe, Jr., James E. Structural Diversity of Ultralong CDRH3s in Seven Bovine Antibody Heavy Chains. Switzerland. doi:https://doi.org/10.3389/fimmu.2019.00558
Dong, Jinhui, Finn, Jessica A., Larsen, Peter A., Smith, Timothy P. L., and Crowe, Jr., James E. Fri . "Structural Diversity of Ultralong CDRH3s in Seven Bovine Antibody Heavy Chains". Switzerland. doi:https://doi.org/10.3389/fimmu.2019.00558.
@article{osti_1503947,
title = {Structural Diversity of Ultralong CDRH3s in Seven Bovine Antibody Heavy Chains},
author = {Dong, Jinhui and Finn, Jessica A. and Larsen, Peter A. and Smith, Timothy P. L. and Crowe, Jr., James E.},
abstractNote = {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.},
doi = {10.3389/fimmu.2019.00558},
journal = {Frontiers in Immunology},
number = ,
volume = 10,
place = {Switzerland},
year = {2019},
month = {3}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
DOI: https://doi.org/10.3389/fimmu.2019.00558

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