Solute uptake through general porins

Abstract

General diffusion porins are among the few membrane proteins that have been thoroughly investigated by many techniques, including X-ray crystallography, AFM microscopy, computer modeling, electrophysiology and biochemistry. This had led to a good understanding of the process of solute transport per se. However, other aspects of porin function remain enigmatic, such as the molecular basis and physiological relevance of many regulatory processes. After summarizing the most salient structural features, the review provides a description of the techniques used for the functional study of porins. The process of solute transport is presented on the basis of structure-function relationship and modeling studies. Three aspects of regulation are discussed: voltage-dependence, pH sensitivity and modulation by polycations and polyanions. The review ends with a perspective on future porin research, to be targeted at a molecular understanding of the regulatory processes, the deciphering of the physiological context in which these processes take place, and rational drug design.

The porin and the permeating antibiotic: a selective diffusion barrier in Gram-negative bacteria

“…This barrier comprises a lipid bilayer that is impermeable to large, charged molecules. Influx is largely controlled by porins, which are water-filled open channels that span the outer membrane and allow the passive penetration of hydrophilic molecules [9][10][11] . Different types of porins have been characterized in Gram-negative bacteria and classified according to their activity (non-specific or specific channel or selective pore), their functional structure (monomeric or trimeric) and their regulation and expression [9][10][11][12][13][14] .…”

“…coli produces three major trimeric porinsOmpF, OmpC and PhoE -and pioneering studies with these porins constitute the foundation of our current knowledge of many other porins 9,10 . Thus, these outer membrane proteins (OMPs) (and their homologues in other Gram-negative bacteria) are termed classical porins 9 .…”

“…Thus, these outer membrane proteins (OMPs) (and their homologues in other Gram-negative bacteria) are termed classical porins 9 . Despite their 'non-specific' nature, the members of this family can be classified according to a range of selective filters with respect to the charge and size of the solutes and charges in key regions of the porin channels: the OmpF and OmpC families show a slight preference for cations, whereas PhoE selects inorganic phosphate and anions [9][10][11][12] . Porins have been purified and reconstituted in various experimental systems (for example, liposomes and planar membranes) to analyse their physico-chemical parameters, such as conductance, selectivity and voltage gating 10 .…”

“…General diffusion porins can be distinguished from the specific and ligand-gated porins by their poor substrate selectivity and their high probability of presenting an open conformation in the absence of any specific substrates 9,10 . Most porins that are involved in antibiotic transport belong to the classical OmpF or OmpC subfamilies.…”

“…For more examples, consult the Transport Protein Database (see Further information). Many aspects of porin activity and physiology have previously been discussed in various reviews [9][10][11][12][13][14][15] .…”