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1.B.21 The OmpG Porin (OmpG) Family

The OmpG family consists of two distantly related functionally characterized E. coli proteins, OmpG and OmpL. The OmpG channel appears to be much larger than the E. coli OmpC or OmpF channels (estimated limited diameter of about 2 nm) (Fajardo et al., 1998). The channel lacks solute specificity, and a folding model suggests a 16-stranded β-barrel porin lacking the large external loop, L3, that constricts the pores in other porins. However, Liang and Tamm (2007) found a 14-stranded β-barrel based on NMR analyses. OmpG has been reconstituted in planar bilayers where it exhibits uniform sized channels. Results suggested that OmpG forms a monomeric rather than the usual trimeric porin (Conlan et al., 2000).  The pH-gating conformations of the beta-barrel have been solved. When the pH changes from neutral to acidic, the flexible extracellular loop L6 folds into and closes the OmpG pore (Damaghi et al. 2010).

Voltage-induced closure occurred in a single step, and channel block by Gd3+ lacked cooperativity seen with trimeric porin OmpF. Incorporation of OmpG into lipid membranes revealing protein-lipid interactions and β-barrel orientation, as sudied by Anbazhagan et al. (2008). OmpG has been intensively studied using physical approaches, providing data on its possible structure and biogenesis (Damaghi et al., 2010; Korkmaz-Ozkan et al., 2010). Refolding pathways of the sequential β-hairpins and kinetics of OmpG folding have been reported (Damaghi et al., 2011).

OmpL has been purified and reconstituted. It allowed diffusion of small solutes including sugars (Dartigalongue et al., 2000). Contrary to an earlier report, it does not influence Dsb-mediated redox potential in the periplasm (Sardesai et al., 2003). The OmpG family is related to the Cyclodextrin Porin (CDP; 1.B.26) and the Oligogalacturonate Porin (KdgM; 1.B.35) families (Condemine et al., 2005). 

β-barrel porins have potential as nanosensors for single-molecule detection. However, they have inflexible biophysical properties and are limited in their pore geometry, hindering their applications in sensing molecules of different sizes and properties. By replacing beta1-beta6 strands of the protein OmpF that lack these motifs with beta1-beta6 strands of OmpG enriched with these motifs and computational verification of increased stability of its transmembrane region, Lin et al. 2017 engineered a novel porin called OmpGF. OmpGF forms a monomer with a stable transmembrane region. It can refold in vitro with a predominant beta-sheet structure, as confirmed by circular dichroism. Evidence of OmpGF membrane insertion was provided by intrinsic tryptophan fluorescence spectroscopy, and its pore-forming property was determined by a dye-leakage assay. Single-channel conductance measurements confirmed that OmpGF function as a monomer and exhibits increased conductance relative to OmpG or OmpF (Lin et al. 2017).

OmpG of E. coli is a robust, monomeric, transmembrane β-barrel without ion selectivity. Kahlstatt et al. 2018 presented a photocaged diethylaminocoumarin (DEACM) hybrid of OmpG. Blockage of the pore by DEACM was confirmed by measuring the reduced conductivity. An optimal effect was obtained when two bulky butyl-substituted coumarin cages were attached on the inside of the pore. Irradiation at 385 nm removed the photocages, leading to a restoration of channel conductivity (Kahlstatt et al. 2018).

References associated with 1.B.21 family:

Anbazhagan, V., J. Qu, J.H. Kleinschmidt, and D. Marsh. (2008). Incorporation of outer membrane protein OmpG in lipid membranes: protein-lipid interactions and β-barrel orientation. Biochemistry 47: 6189-6198. 18473482
Condemine, G., C. Berrier, J. Plumbridge, and A. Ghazi. (2005). Function and expression of an N-acetylneuraminic acid-inducible outer membrane channel in Escherichia coli. J. Bacteriol. 187: 1959-1965. 15743943
Conlan, S., Y. Zhang, S. Cheley, and H. Bayley. (2000). Biochemical and biophysical characterization of OmpG: A monomeric porin. Biochemistry 39: 11845-11854. 11009596
Damaghi, M., C. Bippes, S. Köster, O. Yildiz, S.A. Mari, W. Kühlbrandt, and D.J. Muller. (2010). pH-dependent interactions guide the folding and gate the transmembrane pore of the β-barrel membrane protein OmpG. J. Mol. Biol. 397: 878-882. 20171227
Damaghi, M., K.T. Sapra, S. Köster, &.#.2.1.4.;. Yildiz, W. Kühlbrandt, and D.J. Muller. (2010). Dual energy landscape: the functional state of the β-barrel outer membrane protein G molds its unfolding energy landscape. Proteomics 10: 4151-4162. 21058339
Damaghi, M., S. Köster, C.A. Bippes, O. Yildiz, and D.J. Müller. (2011). One β hairpin follows the other: exploring refolding pathways and kinetics of the transmembrane β-barrel protein OmpG. Angew Chem Int Ed Engl 50: 7422-7424. 21692155
Dartigalongue, C., H. Nikaido, and S. Raina. (2000). Protein folding in the periplasm in the absence of primary oxidant DsbA: modulation of redox poential in periplasmic space via OmpL porin. EMBO J. 19: 5980-5988. 11080145
Fajardo, D.A., J. Cheung, C. Ito, E. Sugawara, H. Nikaido, and R. Misra. (1998). Biochemistry and regulation of a novel Escherichia coli K-12 porin protein, OmpG, which produces unusually large channels. J. Bacteriol. 180: 4452-4459. 9721282
Freeman, T.C., Jr, S.J. Landry, and W.C. Wimley. (2011). The prediction and characterization of YshA, an unknown outer-membrane protein from Salmonella typhimurium. Biochim. Biophys. Acta. 1808: 287-297. 20863811
Grosse, W., G. Psakis, B. Mertins, P. Reiss, D. Windisch, F. Brademann, J. Bürck, A. Ulrich, U. Koert, and L.O. Essen. (2014). Structure-based engineering of a minimal porin reveals loop-independent channel closure. Biochemistry 53: 4826-4838. 24988371
Kahlstatt, J., , P. Reiß, , T. Halbritter, , L.O. Essen, , U. Koert, , and A. Heckel,. (2018). A light-triggered transmembrane porin. Chem Commun (Camb) 54: 9623-9626. 30095845
Korkmaz, F., K. van Pee, and &.#.2.1.4.;. Yildiz. (2015). IR-spectroscopic characterization of an elongated OmpG mutant. Arch Biochem Biophys 576: 73-79. 25958106
Korkmaz-Ozkan, F., S. Köster, W. Kühlbrandt, W. Mäntele, and O. Yildiz. (2010). Correlation between the OmpG secondary structure and its pH-dependent alterations monitored by FTIR. J. Mol. Biol. 401: 56-67. 20561532
Köster, S., K. van Pee, and &.#.2.1.4.;. Yildiz. (2015). Purification, Refolding, and Crystallization of the Outer Membrane Protein OmpG from Escherichia coli. Methods Enzymol 557: 149-166. 25950964
Liang, B., and L.K. Tamm. (2007). Structure of outer membrane protein G by solution NMR spectroscopy. Proc. Natl. Acad. Sci. U.S.A. 104: 16140-16145. 17911261
Lin, M., G. Zhang, M. Fahie, L.K. Morgan, M. Chen, T.A. Keiderling, L.J. Kenney, and J. Liang. (2017). Engineering a novel porin OmpGF via strand replacement from computational analysis of sequence motif. Biochim. Biophys. Acta. [Epub: Ahead of Print] 28341438
Mari, S.A., S. Köster, C.A. Bippes, O. Yildiz, W. Kühlbrandt, and D.J. Muller. (2010). pH-induced conformational change of the β-barrel-forming protein OmpG reconstituted into native E. coli lipids. J. Mol. Biol. 396: 610-616. 20036258
Perez-Rathke, A., M.A. Fahie, C. Chisholm, J. Liang, and M. Chen. (2018). Mechanism of OmpG pH-Dependent Gating from Loop Ensemble and Single Channel Studies. J. Am. Chem. Soc. 140: 1105-1115. 29262680
Retel, J.S., A.J. Nieuwkoop, M. Hiller, V.A. Higman, E. Barbet-Massin, J. Stanek, L.B. Andreas, W.T. Franks, B.J. van Rossum, K.R. Vinothkumar, L. Handel, G.G. de Palma, B. Bardiaux, G. Pintacuda, L. Emsley, W. Kühlbrandt, and H. Oschkinat. (2017). Structure of outer membrane protein G in lipid bilayers. Nat Commun 8: 2073. 29233991
Sardesai, A.A., P. Genevaux, F. Schwager, D. Ang, and C. Georgopoulos. (2003). The OmpL porin does not modulate redox potential in the periplasmic space of Escherichia coli. EMBO J. 22: 1461-1466. 12660153
Schmitt, C., J.A. Bafna, B. Schmid, S. Klingl, S. Baier, B. Hemmis, R. Wagner, M. Winterhalter, and L.M. Voll. (2019). Manipulation of charge distribution in the arginine and glutamate clusters of the OmpG pore alters sugar specificity and ion selectivity. Biochim. Biophys. Acta. Biomembr 1861: 183021. 31306626
Shevchik, V.E. and N. Hugouvieux-Cotte-Pattat. (2003). PaeX, a second pectin acetylesterase of Erwinia chrysanthemi 3937. J. Bacteriol. 185: 3091-3100. 12730169
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