Affiliation:
1. Department of Microbiology and Immunology, Medical College of Virginia at Virginia Commonwealth University
2. Center for the Study of Biological Complexity, Richmond, Virginia 23298-0678
Abstract
ABSTRACT
Borrelia burgdorferi
CspZ (TIGR open reading frame designation, BBH06) is part of a functionally related group of proteins that bind one or more members of the factor H (FH) protein family. In this report we assess the conservation, distribution, properties, and ligand binding abilities of CspZ from the three main
Borrelia
species associated with Lyme disease infections in humans. CspZ (also referred to as BbCRASP-2 in the literature) was found to be highly conserved at the intraspecies level but divergent at the interspecies level. All CspZ orthologs that originated from
B. burgdorferi
isolates bound FH from a diverse group of mammals. In contrast, CspZ derived from
B. garinii
and
B. afzelii
did not. Regardless of the
Borrelia
species of origin, all CspZ proteins tested bound to unknown ∼60-kDa serum proteins produced by different mammals. To further define the molecular basis for the differential binding of CspZ orthologs to host proteins, DNA sequence, truncation, and site-directed mutagenesis analyses were performed. DNA sequence analyses revealed that
B. garinii
and
B. afzelii
CspZ orthologs possess a 64-amino-acid N-terminal domain that is absent from
B. burgdorferi
CspZ. However, binding analyses of recombinant proteins revealed that this domain does not in and of itself influence ligand binding properties. Truncation and mutagenesis analyses further revealed that the key determinants required for ligand binding are discontinuous and that the presentation of the ligand binding pocket is dependent on alpha helices with high coiled-coil formation probability. The data presented here provide insight into the molecular basis of CspZ-ligand interactions and suggest that CspZ orthologs from diverse
Borrelia
species can contribute to the host-pathogen interaction through their interaction with serum proteins.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Cited by
47 articles.
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