Variable Lymphocyte Receptor Recognition of the Immunodominant Glycoprotein of Bacillus anthracis Spores

• Type of Material: Article
• Authors: Robert N. Kirchdoerfer, Scripps Research Institute; Brantley Herrin, Emory University; Byung Woo Han, Seoul National University; Charles L. Turnbough, University of Alabama at Birmingham; Max Dale Cooper, Emory University; Max D. Wilson, Scripps Research Institute
• Language: English
• Date: 2012-03-07
• Publisher: Elsevier (Cell Press)
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2012 Elsevier Ltd All rights reserved.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.str.2012.01.009
• Title of Journal or Parent Work: Structure
• ISSN: 0969-2126
• Volume: 20
• Issue: 3
• Start Page: 479
• End Page: 486
• Grant/Funding Information: The Advanced Light Source is supported by the Director, Office of Science, Office of Basic Energy Sciences, U.S. Department of Energy under Contract No. DE-AC02-05CH11231.; Use of the Advanced Photon Source was supported by the U.S. Department of Energy, Basic Energy Sciences, Office of Science, under contract No. DE-AC02-06CH11357. The Berkeley Center for Structural Biology is supported in part by the National Institutes of Health, National Institute of General Medical Sciences, and the Howard Hughes Medical Institute.; Support is acknowledged from NIH AI042266 to IAW, AI081777 to CLT, and AI072435 to MDC, and the Basic Science Research Program (2011-0027449) and the Global Frontier (NRF-M1AXA002-2010-0029770) through the National Research Foundation of Korea to BWH. GM/CA CAT has been funded in whole or in part with Federal funds from the National Cancer Institute (Y1-CO-1020) and the National Institute of General Medical Sciences (Y1-GM-1104).
• Keywords: Biophysics; Biochemistry & Molecular Biology; IDENTIFICATION; EXOSPORIUM; Science & Technology; DIVERSIFICATION; ANTIGEN RECOGNITION; BCLA; COLLAGEN-LIKE REGION; PROTEIN; MONOCLONAL-ANTIBODIES; SEA LAMPREY; MAXIMUM-LIKELIHOOD; Life Sciences & Biomedicine; Cell Biology
• Research Categories: Health Sciences, Pathology

Abstract

Variable lymphocyte receptors (VLRs) are the adaptive immune receptors of jawless fish, which evolved adaptive immunity independent of other vertebrates. In lieu of the immunoglobulin fold-based T and B cell receptors, lymphocyte-like cells of jawless fish express VLRs (VLRA, VLRB, or VLRC) composed of leucine-rich repeats and are similar to toll-like receptors (TLRs) in structure, but antibodies (VLRB) and T cell receptors (VLRA and VLRC) in function. Here, we present the structural and biochemical characterization of VLR4, a VLRB, in complex with BclA, the immunodominant glycoprotein of Bacillus anthracis spores. Using a combination of crystallography, mutagenesis, and binding studies, we delineate the mode of antigen recognition and binding between VLR4 and BclA, examine commonalities in VLRB recognition of antigens, and demonstrate the potential of VLR4 as a diagnostic tool for the identification of B. anthracis spores.