2lfu
From Proteopedia
The structure of a N. meningitides protein targeted for vaccine development
Structural highlights
FunctionNHBA_NEIME A major human immunogenic protein detected in patients recovering from meningitidis, where it induces bactericidal antibodies (PubMed:30133484) (By similarity). Binds human cells, heparin and heparan sulfate proteoglycan in vitro via the Arg-rich motif. Heparin-binding to this protein protects bacteria against killing by bactericidal antibodies (serum killing). The bacteria binds a number of human extracellular sialyated and/or sulfated glycans via this protein, including chondroitin sulfate, heparin and ganglioside GT3. Binds DNA non-specifically (By similarity).[UniProtKB:Q7DD37][1] May play a role in extracellular-DNA (eDNA) mediated biofilm formation. When NHBA is not processed by NalP there is an increase in biofilm formation (PubMed:23163582). Lack of processing may lead to an increase in positively charged, NHBA- and IgA-derived DNA-binding peptides on the cell surface, resulting in increased DNA-binding peptides and increased biofilm formation (Probable).[2] [3] Publication Abstract from PubMedNeisseria heparin binding antigen (NHBA), also known as GNA2132 (genome-derived Neisseria antigen 2132), is a surface-exposed lipoprotein from Neisseria meningitidis that was originally identified by reverse vaccinology. It is one the three main antigens of a multicomponent vaccine against serogroup B meningitis (4CMenB), which has just completed phase III clinical trials in infants. In contrast to the other two main vaccine components, little is known about the origin of the immunogenicity of this antigen, and about its ability to induce a strong cross-bactericidal response in animals and humans. To characterize NHBA in terms of its structural/immunogenic properties, we have analyzed its sequence and identified a C-terminal region that is highly conserved in all strains. We demonstrate experimentally that this region is independently folded, and solved its three-dimensional structure by nuclear magnetic resonance. Notably, we need detergents to observe a single species in solution. The NHBA domain fold consists of an 8-strand beta-barrel that closely resembles the C-terminal domains of N. meningitidis factor H-binding protein and transferrin-binding protein B. This common fold together with more subtle structural similarities suggest a common ancestor for these important antigens and a role of the beta-barrel fold in inducing immunogenicity against N. meningitidis. Our data represent the first step toward understanding the relationship between structural, functional, and immunological properties of this important vaccine component. Structure of the C-terminal Domain of Neisseria Heparin Binding Antigen (NHBA), One of the Main Antigens of a Novel Vaccine against Neisseria meningitidis.,Esposito V, Musi V, de Chiara C, Veggi D, Serruto D, Scarselli M, Kelly G, Pizza M, Pastore A J Biol Chem. 2011 Dec 2;286(48):41767-75. Epub 2011 Sep 29. PMID:21965688[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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