RGD Reference Report - Deciphering the interface between a CD40 receptor and borrelial ligand OspA. - Rat Genome Database

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Deciphering the interface between a CD40 receptor and borrelial ligand OspA.

Authors: Mlynarcik, P  Pulzova, L  Bencurova, E  Kovac, A  Dominguez, MA  Hresko, S  Bhide, MR 
Citation: Mlynarcik P, etal., Microbiol Res. 2015 Jan;170:51-60. doi: 10.1016/j.micres.2014.09.003. Epub 2014 Sep 19.
RGD ID: 11344975
Pubmed: PMID:25260678   (View Abstract at PubMed)
DOI: DOI:10.1016/j.micres.2014.09.003   (Journal Full-text)

Neuroborreliosis is serious sequelae of Lyme borreliosis. Neuroinvasion is largely relied on successful translocation of Borrelia across the blood-brain barrier. Adherence of Borrelia to brain microvascular endothelial cell (BMEC) seems to be critical for translocation. Here we unfold the interface between OspA and CD40 molecules, major ligand and receptor, that are involved in adhesion of Borrelia to BMECs. We found that a region between Asn127 and Asp205 of OspA forms the CD40-receptor binding site. This region encompasses human umbilical vein endothelial cell (HUVEC) binding domain and contains a potential ligand-binding pocket lined by three amino acid residues: Arg139, Glu160 and Lys189. Disruption of this pocket (by truncation of the HUVEC binding domain) caused complete abrogation of its ability to bind CD40. To identify the amino acid residues within the HUVEC binding domain involved in the CD40 binding, site-directed mutagenesis and binding assays were performed. Results showed that Asp149, Phe165, Ala172, Val186 and Leu192 might form interface with CD40 molecule. Other side of the interface was also identified with the help of a ligand-binding assay with OspA and truncated CD40 fragments. Results exposed that cysteine rich domain 2 (CRD2) of CD40 might be the site for OspA binding. Precise knowledge of the molecular basis of the ligand-receptor interactions is essential in order to understand mechanisms of pathogenesis and could help in the development of novel therapeutics and vaccines.



Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Cd40Ratprotein domain specific binding  IPIUniProtKB:Q04968 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cd40  (CD40 molecule)


Additional Information