Structural requirements for proinflammatory activity of porin P2 loop 7 from Haemophilus influenzae(731 views) Galdiero S, Vitiello M, Amodeo P, D'Isanto M, Cantisani M, Pedone C, Galdiero M
Department of Experimental Medicine, II University of Naples, Via De Crecchio 7, 80138 Naples, Italy
Department of Biological Sciences, University of Naples Federico II, Istituto di Biostrutture e Bioimmagini-CNR, Via Mezzocannone 16, 80134 Naples, Italy
Istituto di Chimica Biomolecolare-CNR, Sede di Pozzuoli, Comprensorio Olivetti, Via Campi Flegrei 34, 80078 Pozzuoli, Naples, Italy
References: Not available.
Structural requirements for proinflammatory activity of porin P2 loop 7 from Haemophilus influenzae
Haemophilus influenzae type b (Hib) is one of the leading causes of invasive bacterial infection in young children, characterized by inflammation 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. Synthetic peptides corresponding to loops L5, L6, and L7 activate JNK and p38 mitogen-activated protein kinase (MAPK) pathways, L7 being the most active peptide. Therefore, sequence-activity relationships and key residues were identified by elongating sequence to different extents, designing cyclic peptides, and performing an alanine scan of L7. The ability of mutant peptides to induce activation of signal transduction pathways and release of TNF-alpha and IL-6 has been determined, and, in conjunction with CD spectra, bioinformatics analysis, and molecular dynamics data, showed that 6 out of 8 amino acids contribute significantly to the overall activity. Molecular dynamics showed that L7 modifications increased loop rigidity and helicity after Gly6 mutation, thus, providing a possible structural explanation for observed loss of bioactivity. This work provides insights into essential molecular details of P2 that may impact on the pathogenesis of Hib infections where interruption of the signaling cascade could represent an attractive therapeutic strategy.
Structural requirements for proinflammatory activity of porin P2 loop 7 from Haemophilus influenzae
Kállay C, Dávid A, Timári S, Nagy EM, Sanna D, Garribba E, Micera G, De Bona P, Pappalardo G, Rizzarelli E, Sóvágó I * Copper(II) complexes of rat amylin fragments(569 views) Dalton T (ISSN: 1477-9234, 1477-9226, 1477-9234electronic), 2011 Oct 14; 40(38): 9711-9721. Impact Factor:3.838 ViewExport to BibTeXExport to EndNote