Some known structures of β-barrel membrane proteins

The integral membrane proteins with β-barrel structures are known from outer membranes of bacteria, mitochondria, and chloroplasts. The β-barrel is characterized by the number of antiparallel β-strands and by the shear number,  which is a measure for the inclination angle of the β-strands against the barrel axis. The outer membrane proteins (OMPs) of bacteria form transmembrane β-barrels with even numbers of β-strands ranging from 8 to 22 with shear numbers from 8-24 [1]. The strands are tilted by 36° to 44° relative to the barrel axis [1, 2]. Examples are OmpA [3, 4], OmpX [5-7], NspA [8], and PagP [9, 10] (8 β-strands); OmpT [11] (10 β-strands); NalP [12] and OmPlA [13]  (12 β-strands); FadL [14] (14 β-strands); Omp32 [15], matrix porin [16], OmpF [17], and PhoE [18] (16 β-strands); maltoporin (LamB) [19] and sucrose porin (ScrY) [20] (18 β-strands); FepA [21], BtuB [22, 23], and FhuA [24, 25] (22 β-strands). Monomers (OmpA, FhuA, OmpG [26]), dimers (OmPlA) and trimers (OmpF, PhoE) are known. β-barrel membrane proteins serve a wide range of different functions. They can be non-specific diffusion pores (OmpA, OmpC, OmpF), specific pores (LamB, ScrY), active transporters (FhuA, FepA, BtuB), enzymes such as proteases (OmpT), lipases (OmPlA), acyltransferases (PagP), or, like TolC, involved in solute efflux [27]. Some examples of β-barrel membrane proteins are shown above.

OmpA is a small ion channel [28], OmpT is a protease, NalP is an autotransporter, FadL is a long chain fatty acid transporter, PhoE is a diffusion pore, ScrY is a sucrose specific porin, OmPlA is a phospholipase. FhuA and BtuB are active transporters for ferrichrom iron and vitamin B12 uptake, respectively. OMPs of mitochondria are predicted to form similar TM β-barrels. Examples are the VDAC channels, out of which more than a dozen have been sequenced [29]. The membrane protein structures shown above were generated with MolMol [30].

Recently developed screening algorithms for the genomic identification of β-barrel membrane proteins indicate that there are many still not characterized outer membrane proteins for example in the genomes of E. coli and P. aeruginosa [31, 32]. Soluble bacterial toxins that can insert into membranes, such as α-hemolysine from Staphylococcus aureus [33], perfringolysine O from Clostridium perfringens [34, 35] also form β-barrels, but these are oligomeric.

See also

Kleinschmidt, J.H. 2005, Folding and Stability of monomeric β-barrel Membrane proteins In: Protein-Lipid Interactions, Ed. Tamm, L.K. John Wiley & Sons 


1. Schulz GE: The structure of bacterial outer membrane proteins. Biochim Biophys Acta 2002, 1565(2):308-317.

2. Marsh D, Pali T: Infrared dichroism from the X-ray structure of bacteriorhodopsin. Biophys J 2001, 80(1):305-312.

3. Arora A, Abildgaard F, Bushweller JH, Tamm LK: Structure of outer membrane protein A transmembrane domain by NMR spectroscopy. Nature Structural Biology 2001, 8(4):334-338.

4. Pautsch A, Schulz GE: High-resolution structure of the OmpA membrane domain. Journal of Molecular Biology 2000, 298(2):273-282.

5. Vogt J, Schulz GE: The structure of the outer membrane protein OmpX from Escherichia coli reveals possible mechanisms of virulence. Structure Fold Des 1999, 7(10):1301-1309.

6. Fernandez C, Adeishvili K, Wuthrich K: Transverse relaxation-optimized NMR spectroscopy with the outer membrane protein OmpX in dihexanoyl phosphatidylcholine micelles. Proc Natl Acad Sci U S A 2001, 98(5):2358-2363.

7. Hilty C, Wider G, Fernandez C, Wuthrich K: Membrane protein-lipid interactions in mixed micelles studied by NMR spectroscopy with the use of paramagnetic reagents. Chembiochem 2004, 5(4):467-473.

8. Vandeputte-Rutten L, Bos MP, Tommassen J, Gros P: Crystal structure of Neisserial surface protein A (NspA), a conserved outer membrane protein with vaccine potential. J Biol Chem 2003, 278(27):24825-24830.

9. Hwang PM, Choy WY, Lo EI, Chen L, Forman-Kay JD, Raetz CR, Prive GG, Bishop RE, Kay LE: Solution structure and dynamics of the outer membrane enzyme PagP by NMR. Proc Natl Acad Sci U S A 2002, 99(21):13560-13565.

10. Ahn VE, Lo EI, Engel CK, Chen L, Hwang PM, Kay LE, Bishop RE, Prive GG: A hydrocarbon ruler measures palmitate in the enzymatic acylation of endotoxin. Embo J 2004, 23(15):2931-2941.

11. Vandeputte-Rutten L, Kramer RA, Kroon J, Dekker N, Egmond MR, Gros P: Crystal structure of the outer membrane protease OmpT from Escherichia coli suggests a novel catalytic site. Embo J 2001, 20(18):5033-5039.

12. Oomen CJ, Van Ulsen P, Van Gelder P, Feijen M, Tommassen J, Gros P: Structure of the translocator domain of a bacterial autotransporter. Embo J 2004, 23(6):1257-1266.

13. Snijder HJ, Ubarretxena-Belandia I, Blaauw M, Kalk KH, Verheij HM, Egmond MR, Dekker N, Dijkstra BW: Structural evidence for dimerization-regulated activation of an integral membrane phospholipase. Nature 1999, 401(6754):717-721.

14. van den Berg B, Black PN, Clemons WM, Jr., Rapoport TA: Crystal structure of the long-chain fatty acid transporter FadL. Science 2004, 304(5676):1506-1509.

15. Zeth K, Diederichs K, Welte W, Engelhardt H: Crystal structure of Omp32, the anion-selective porin from Comamonas acidovorans, in complex with a periplasmic peptide at 2.1 A resolution. Structure Fold Des 2000, 8(9):981-992.

16. Weiss MS, Kreusch A, Schiltz E, Nestel U, Welte W, Weckesser J, Schulz GE: The structure of porin from Rhodobacter capsulatus at 1.8 A resolution. FEBS Lett 1991, 280(2):379-382.

17. Cowan SW, Garavito RM, Jansonius JN, Jenkins JA, Karlsson R, Konig N, Pai EF, Pauptit RA, Rizkallah PJ, Rosenbusch JP et al: The structure of OmpF porin in a tetragonal crystal form. Structure with Folding and Design 1995, 3(10):1041-1050.

18. Cowan SW, Schirmer T, Rummel G, Steiert M, Ghosh R, Pauptit RA, Jansonius JN, Rosenbusch JP: Crystal structures explain functional properties of two E. coli porins. Nature 1992, 358(6389):727-733.

19. Schirmer T, Keller TA, Wang YF, Rosenbusch JP: Structural basis for sugar translocation through maltoporin channels at 3.1 A resolution. Science 1995, 267(5197):512-514.

20. Forst D, Welte W, Wacker T, Diederichs K: Structure of the sucrose-specific porin ScrY from Salmonella typhimurium and its complex with sucrose. Nature Structural Biology 1998, 5(1):37-46.

21. Buchanan SK, Smith BS, Venkatramani L, Xia D, Esser L, Palnitkar M, Chakraborty R, van der Helm D, Deisenhofer J: Crystal structure of the outer membrane active transporter FepA from Escherichia coli. Nat Struct Biol 1999, 6(1):56-63.

22. Chimento DP, Mohanty AK, Kadner RJ, Wiener MC: Crystallization and initial X-ray diffraction of BtuB, the integral membrane cobalamin transporter of Escherichia coli. Acta Crystallogr D Biol Crystallogr 2003, 59(Pt 3):509-511.

23. Kurisu G, Zakharov SD, Zhalnina MV, Bano S, Eroukova VY, Rokitskaya TI, Antonenko YN, Wiener MC, Cramer WA: The structure of BtuB with bound colicin E3 R-domain implies a translocon. Nat Struct Biol 2003, 10(11):948-954.

24. Ferguson AD, Hofmann E, Coulton JW, Diederichs K, Welte W: Siderophore-mediated iron transport: crystal structure of FhuA with bound lipopolysaccharide. Science 1998, 282(5397):2215-2220.

25. Locher KP, Rees B, Koebnik R, Mitschler A, Moulinier L, Rosenbusch JP, Moras D: Transmembrane signaling across the ligand-gated FhuA receptor: crystal structures of free and ferrichrome-bound states reveal allosteric changes. Cell 1998, 95(6):771-778.

26. Conlan S, Zhang Y, Cheley S, Bayley H: Biochemical and biophysical characterization of OmpG: A monomeric porin. Biochemistry 2000, 39(39):11845-11854.

27. Koronakis V, Sharff A, Koronakis E, Luisi B, Hughes C: Crystal structure of the bacterial membrane protein TolC central to multidrug efflux and protein export. Nature 2000, 405(6789):914-919.

28. Arora A, Rinehart D, Szabo G, Tamm LK: Refolded outer membrane protein A of Escherichia coli forms ion channels with two conductance states in planar lipid bilayers. Journal of Biological Chemistry 2000, 275(3):1594-1600.

29. Heins L, Mentzel H, Schmid A, Benz R, Schmitz UK: Biochemical, molecular, and functional characterization of porin isoforms from potato mitochondria. Journal of Biological Chemistry 1994, 269(42):26402-26410.

30. Koradi R, Billeter M, Wuthrich K: MOLMOL: a program for display and analysis of macromolecular structures. J Mol Graph 1996, 14(1):51-55, 29-32.

31. Wimley WC: Toward genomic identification of beta-barrel membrane proteins: composition and architecture of known structures. Protein Sci 2002, 11(2):301-312.

32. Wimley WC: The versatile beta-barrel membrane protein. Curr Opin Struct Biol 2003, 13(4):404-411.

33. Song L, Hobaugh MR, Shustak C, Cheley S, Bayley H, Gouaux JE: Structure of staphylococcal alpha-hemolysin, a heptameric transmembrane pore. Science 1996, 274(5294):1859-1866.

34. Heuck AP, Hotze EM, Tweten RK, Johnson AE: Mechanism of membrane insertion of a multimeric beta-barrel protein: perfringolysin O creates a pore using ordered and coupled conformational changes. Mol Cell 2000, 6(5):1233-1242.

35. Shepard LA, Heuck AP, Hamman BD, Rossjohn J, Parker MW, Ryan KR, Johnson AE, Tweten RK: Identification of a membrane-spanning domain of the thiol-activated pore-forming toxin Clostridium perfringens perfringolysin O: an alpha-helical to beta-sheet transition identified by fluorescence spectroscopy. Biochemistry 1998, 37(41):14563-14574.