Title
Structural and molecular analysis of a protective epitope of Lyme disease antigen OspA and antibody interactions
UMMS Affiliation
Department of Biochemistry and Molecular Pharmacology; MassBiologics
Publication Date
2016-11-16
Document Type
Article
Disciplines
Bacterial Infections and Mycoses | Biochemistry | Immunoprophylaxis and Therapy | Medicinal Chemistry and Pharmaceutics | Medicinal-Pharmaceutical Chemistry | Molecular Biology | Structural Biology
Abstract
The murine monoclonal antibody LA-2 recognizes a clinically protective epitope on outer surface protein (OspA) of Borrelia burgdorferi, the causative agent of Lyme disease in North America. Human antibody equivalence to LA-2 is the best serologic correlate of protective antibody responses following OspA vaccination. Understanding the structural and functional basis of the LA-2 protective epitope is important for developing OspA-based vaccines and discovering prophylactic antibodies against Lyme disease. Here, we present a detailed structure-based analysis of the LA-2/OspA interaction interface and identification of residues mediating antibody recognition. Mutations were introduced into both OspA and LA-2 on the basis of computational predictions on the crystal structure of the complex and experimentally tested for in vitro binding and borreliacidal activity. We find that Y32 and H49 on the LA-2 light chain, N52 on the LA-2 heavy chain and residues A208, N228 and N251 on OspA were the key constituents of OspA/LA-2 interface. These results reveal specific residues that may be exploited to modulate recognition of the protective epitope of OspA and have implications for developing prophylactic passive antibodies.
Keywords
antibody, Lyme disease, mutations, protein-protein, structural analysis, molecular interactions, vaccine design, protein structure, UMCCTS funding
DOI of Published Version
10.1002/jmr.2595
Source
J Mol Recognit. 2016 Nov 16. doi: 10.1002/jmr.2595. Link to article on publisher's site
Journal/Book/Conference Title
Journal of molecular recognition : JMR
Related Resources
PubMed ID
27859766
Repository Citation
Shandilya, Shivender; Yilmaz, Nese Kurt; Sadowski, Andrew; Monir, Ejemel; Schiller, Zachary A.; Thomas, William D. Jr.; Klempner, Mark S.; Schiffer, Celia A.; and Wang, Yang, "Structural and molecular analysis of a protective epitope of Lyme disease antigen OspA and antibody interactions" (2016). Schiffer Lab Publications. 14.
https://escholarship.umassmed.edu/schiffer/14