title: Why do the outer membrane proteins OmpF from E. coli and OprP from P. aeruginosa prefer trimers? Simulation studies.
abstract: Porins are water-filled protein channels across the outer membrane of gram-negative bacteria. They facilitate the uptake of nutrients and essential ions. Solutes are filtered by a constriction loop L3 at the mid of a pore. Porins are heat-stable and resistant to toxic agents and detergents. Most porins are trimer, but no clear explanation why trimeric form is preferable. In this work, we thus studied effects of oligomerization on porin structure and function in microscopic detail. A well-studied OmpF (general porin from Escherichia coli) and well-characterised OprP (phosphate-specific pore from Pseudomonas aeruginosa) are used as samples from 2 types of porins found in gram-negative bacteria. MD simulations of trimeric and monomeric pores in pure water and 1M NaCl solution were performed. With a salt solution, the external electric field was applied to mimic a transmembrane potential. Expectedly, OprP is more stable than OmpF. Interestingly, being a monomer turns OmpF into an anion-selective pore. The dislocation of D113's side chain on L3 in OmpF causes the disruption of cation pathway resulting in the reduction of cation influx. In contrast, OprP's structure and function are less dependent on oligomeric states. Both monomeric and trimeric OprP can maintain their anion selectivity. Our findings suggest that trimerization is crucial for both structure and function of general porin OmpF, whereas being trimer in substrate-specific channel OprP supports a pore function.
authors.affiliation: Department of Computer engineering, Faculty of Engineering, Kasetsart Univeristy, Chatuchak, Bangkok 10900, Thailand.
authors.forename: Jitti
authors.initials: J
authors.lastname: Niramitranon
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: Mark S P
authors.initials: MS
authors.lastname: Sansom
authors.affiliation: Department of Chemistry, Faculty of Science, Kasetsart University, Chatuchak, Bangkok 10900, Thailand. Electronic address: fsciprpo@ku.ac.th.
authors.forename: Prapasiri
authors.initials: P
authors.lastname: Pongprayoon
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D030562:Databases, Protein; D004926:Escherichia coli / Q000737:chemistry* / Q000378:metabolism; D015870:Gene Expression; D006860:Hydrogen Bonding; D056004:Molecular Dynamics Simulation; D018272:Porins / Q000737:chemistry* / Q000378:metabolism; D000072417:Protein Domains; D055503:Protein Multimerization; D055550:Protein Stability; D017433:Protein Structure, Secondary; D011550:Pseudomonas aeruginosa / Q000737:chemistry* / Q000378:metabolism; D012965:Sodium Chloride / Q000737:chemistry; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
chemical_list: D001426:Bacterial Proteins; C109237:OmpF protein; D018272:Porins; C065416:oprP protein, Pseudomonas aeruginosa; D014867:Water; D012965:Sodium Chloride
keywords: Molecular dynamics simulations; OmpF; OprP; Outer membrane protein; Porin; Trimer