title: A novel transport mechanism for MOMP in Chlamydophila pneumoniae and its putative role in immune-therapy.
abstract: Major outer membrane proteins (MOMPs) of Gram negative bacteria are one of the most intensively studied membrane proteins. MOMPs are essential for maintaining the structural integrity of bacterial outer membranes and in adaptation of parasites to their hosts. There is evidence to suggest a role for purified MOMP from Chlamydophila pneumoniae and corresponding MOMP-derived peptides in immune-modulation, leading to a reduced atherosclerotic phenotype in apoE(-/-) mice via a characteristic dampening of MHC class II activity. The work reported herein tests this hypothesis by employing a combination of homology modelling and docking to examine the detailed molecular interactions that may be responsible. A three-dimensional homology model of the C. pneumoniae MOMP was constructed based on the 14 transmembrane β-barrel crystal structure of the fatty acid transporter from Escherichia coli, which provides a plausible transport mechanism for MOMP. Ligand docking experiments were used to provide details of the possible molecular interactions driving the binding of MOMP-derived peptides to MHC class II alleles known to be strongly associated with inflammation. The docking experiments were corroborated by predictions from conventional immuno-informatic algorithms. This work supports further the use of MOMP in C. pneumoniae as a possible vaccine target and the role of MOMP-derived peptides as vaccine candidates for immune-therapy in chronic inflammation that can result in cardiovascular events.
authors: School of Biological Sciences, Whiteknights Campus, University of Reading, Reading, Berkshire, United Kingdom.
authors: Francis O
authors: FO
authors: Atanu
authors: Ernesto
authors: E
authors: Oviedo-Orta
authors: Kimberly A
authors: KA
authors: Watson
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D001692:Biological Transport; D023521:Chlamydophila Infections / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D016993:Chlamydophila pneumoniae / Q000276:immunology / Q000378:metabolism*; D015804:HLA-DR4 Antigen / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D007167:Immunotherapy; D051379:Mice; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D015203:Reproducibility of Results; D016415:Sequence Alignment
chemical_list: D001425:Bacterial Outer Membrane Proteins; D015804:HLA-DR4 Antigen; D000949:Histocompatibility Antigens Class II; D010455:Peptides; C101031:major outer membrane protein, Chlamydia pneumoniae
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