Peptides complementary to the active loop of porin P2 from Haemophilus influenzae modulate its activity.
Haemophilus influenzae type b (Hib) is one of the leading causes of invasive bacterial infection in young children. It is characterized by inflammation that is mainly mediated by cytokines and chemokines. One of the most abundant components of the Hib outer membrane is the P2 porin, which has been shown to induce the release of several inflammatory cytokines. A synthetic peptide corresponding to loop L7 of the porin activates JNK and p38 mitogen-activated protein kinase (MAPK) pathways. We report a novel use of the complementary peptide approach to design a peptide that is able to bind selectively to the protein P2, thereby reducing its activity. This work provides insights into essential molecular details of P2 that may affect the pathogenesis of Hib infections where interruption of the signaling cascade could represent an attractive therapeutic strategy.
Department of Biological Sciences, CIRPeB and IBB CNR, University of Naples "Federico II," Napoli, Italy.
Marco
M
Cantisani
Mariateresa
M
Vitiello
Annarita
A
Falanga
Emiliana
E
Finamore
Marilena
M
Galdiero
Stefania
S
Galdiero
D000465:Algorithms; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism*; D020134:Catalytic Domain / Q000187:drug effects*; D002850:Chromatography, Gel; D006193:Haemophilus influenzae; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D018272:Porins / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D012486:Salmonella typhimurium; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D020298:U937 Cells
D001426:Bacterial Proteins; C508600:IL6 protein, human; D015850:Interleukin-6; D016328:NF-kappa B; C113724:OmpC protein; D010455:Peptides; D018272:Porins; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; C451502:ompP2 protein, Haemophilus influenzae