Structural highlights
Publication Abstract from PubMedFactor H binding protein (fHbp) is an important antigen of Neisseria meningitidis that is able to elicit a robust protective immune response in humans. Previous studies on the interactions of fHbp with antibodies revealed that some anti-fHbp monoclonal antibodies that are unable to trigger complement-mediated bacterial killing in vitro , are highly cooperative and become bactericidal if used in combination. Several factors have been shown to influence such cooperativity, including IgG subclass and antigen density. To investigate the structural basis of the anti-fHbp antibody synergy, we determined the crystal structure of the complex between fHbp and the Fab fragment of JAR5, a specific anti-fHbp murine monoclonal antibody known to be highly cooperative with other monoclonal antibodies. We show that JAR5 is highly synergic with mAb 12C1, whose structure in complex with fHbp has been previously solved. Structural analyses of the epitopes recognized by JAR5 and 12C1, and computational modelling of full-length IgG mAbs of JAR5 and 12C1 bound to the same fHbp molecule provide insights on the spatial orientation of Fc regions and on the possible implications for the susceptibility of meningococci to complement-mediated killing. Neisseria meningitidis fac---tor H bin---ding protein bound to monoclonal antibody JAR5: implications for antibody synergy.,Malito E, Lo Surdo P, Veggi D, Santini L, Heather Stefek H, Brunelli B, Luzzi E, Bottomley MJ, Beernink P, Scarselli M Biochem J. 2016 Oct 26. pii: BCJ20160806. PMID:27784765[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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