Skip to main content
PMC home page
Springer Nature - PMC COVID-19 Collection logoLink to Springer Nature - PMC COVID-19 Collection
. 1995;143(3):177–188. doi: 10.1007/BF00233446

Predictive evidence for a porin-type β-barrel fold in CHIP28 and other members of the MIP family. A restricted-pore model common to water channels and facilitators

J Fischbarg 1, J Li 1, M Cheung 1, F Czegledy 1, P Iserovich 1, K Kuang 1
PMCID: PMC7087546  PMID: 7539497

Abstract

Water channels are the subject of much current attention, as they may be central for cell functions in a host of tissues. We have analyzed the possible fold of facilitators and water channels of the MIP family based on structural predictions, on findings about the topology of CHIP28, and on the biophysical characteristics of water channels. We developed predictions for the following proteins: MIP26, NOD26, GLP, BIB, γ-TIP, FA-CHIP, CHIP28k, WCH-CD1, and CHIP28. We utilized Kyte Doolittle hydrophobicity, Eisenberg's amphiphilicity, Chou-Fasman-Prevelige propensities, and our own Union algorithm. We found that hydrophobic amphiphilic segments likely to be transmembrane were consistently shorter than required for α-helical segments, but of the correct length for β-strands. Turn propensity was high at frequent intervals, consistent with transmembrane β-strands. We propose that these proteins fold as porin-like 16-stranded antiparallel β-barrels. In water channels, from the size of molecules excluded, an extramembrane loop(s) would enter the pore and restrict it to a bottleneck with a width 4 Å ⩽w ⩽5 Å. A similar but more mobile loop(s) would act as gate and binding site for the facilitators of the MIP family.

Key words: Membrane proteins, Facilitators, Water channels, MIP protein family, Protein structure prediction

References

  1. Abrami L., Simon M., Rousselet G., Berthonaud V., Buhler J.M., Ripoche P. Sequence and functional expression of an amphibian water channel, FA-CHIP: a new member of the CHIP family. Biochim. Biophys. Acta. 1994;1192:147–151. doi: 10.1016/0005-2736(94)90155-4. [DOI] [PubMed] [Google Scholar]
  2. Agre P., Preston G.M., Smith B.L., Jung J.S., Raina S., Moon C., Guggino W.B., Nielsen S. Aquaporin CHIP: the archetypal molecular water channel. Am. J. Physiol. 1993;265:F463–F476. doi: 10.1152/ajprenal.1993.265.4.F463. [DOI] [PubMed] [Google Scholar]
  3. Chepelinsky A.B. The MIP transmembrane channel family. In: Peracchia C., editor. Handbook of membrane channels: molecular and cellular physiology. San Diego, CA: Academic Press; 1994. pp. 413–432. [Google Scholar]
  4. Cowan S.W., Rosenbusch J.P. Folding pattern diversity of integral membrane proteins. Science. 1994;264:914–916. doi: 10.1126/science.8178151. [DOI] [PubMed] [Google Scholar]
  5. Cowan S.W., Shirmer T., Rummel G., Steiert M., Ghosh R., Pauptit R.A., Jansonius J.N., Rosenbusch J.P. Crystal structures explain functional properties of two E. coli porins. Nature. 1992;358:727–733. doi: 10.1038/358727a0. [DOI] [PubMed] [Google Scholar]
  6. Eisenberg D., Weiss R.M., Terwilliger T.C. The hydrophobic moment detects periodicity in protein hydrophobicity. Proc. Natl. Acad. Sci. USA. 1984;81:140–144. doi: 10.1073/pnas.81.1.140. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fischbarg J., Cheung M., Czegledy F., Li J., Iserovich P., Kuang K., Hubbard J., Garner M, Rosen O.M., Golde D.W., Vera J.C. Evidence that facilitative glucose transporters may fold as beta-barrels. Proc. Natl. Acad. Sci. USA. 1993;90:11658–11662. doi: 10.1073/pnas.90.24.11658. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fischbarg J., Cheung M., Li J., Iserovich P., Czegledy F., Kuang K., Garner M. Are most transporters and channels beta barrels? Mol. Cell. Biochem. 1994;140:147–162. doi: 10.1007/BF00926753. [DOI] [PubMed] [Google Scholar]
  9. Fushimi K., Uchida S., Hara Y., Hirata Y., Marumo F., Sasaki S. Cloning and expression of apical membrane water channel of rat kidney collecting tubule. Nature. 1993;361:549–552. doi: 10.1038/361549a0. [DOI] [PubMed] [Google Scholar]
  10. Hasegawa H., Zhang R., Dohrman A., Verkman A.S. Tissue-specific expression of mRNA encoding rat kidney water channel CHIP28k by in situ hybridization. Am. J. Physiol. 1993;264:C237–C245. doi: 10.1152/ajpcell.1993.264.1.C237. [DOI] [PubMed] [Google Scholar]
  11. Hays R.M., Leaf A. Studies on the movement of water through the isolated toad bladder and its modification by vasopressin. J. Gen. Physiol. 1962;45:905–919. doi: 10.1085/jgp.45.5.905. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Jung J.S., Preston G.M., Smith B.L., Guggino W.B., Agre P. Molecular structure of the water channel through aquaporin CHIP. The hourglass model. J. Biol. Chem. 1994;269:14648–14654. [PubMed] [Google Scholar]
  13. Kyte J., Doolittle R.F. A simple method for displaying the hydropathic character of a protein. J. Mol. Biol. 1982;157:105–132. doi: 10.1016/0022-2836(82)90515-0. [DOI] [PubMed] [Google Scholar]
  14. Macey R.I. Transport of water and urea in red blood cells. Am. J. Physiol. 1984;246:C195–C203. doi: 10.1152/ajpcell.1984.246.3.C195. [DOI] [PubMed] [Google Scholar]
  15. Macey R.I., Farmer R.E.L. Inhibition of water and solute permeability in human red cells. Biochim. Biophys. Acta. 1970;211:104–106. doi: 10.1016/0005-2736(70)90130-6. [DOI] [PubMed] [Google Scholar]
  16. Maurel C., Reizer J., Schroeder J.I., Chrispeels M.J. The vacuolar membrane protein g-TIP creates water specific channels in Xenopus oocytes. The EMBO Journal. 1993;12:2241–2247. doi: 10.1002/j.1460-2075.1993.tb05877.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Muramatsu S., Mizuno T. Nucleotide sequence of the region encompassing the glpKF operon and its upstream region containing a bent DNA sequence of Escherichia coli. Nucl. Acids Res. 1989;17:4378. [PMC free article] [PubMed] [Google Scholar]
  18. Nielsen S., Smith B.L., Christensen E.I., Knepper M.A., Agre P. CHIP28 water channels are localized in constitutively water-permeable segments of the nephron. J. Cell Biol. 1993;120:371–383. doi: 10.1083/jcb.120.2.371. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Parisi M., Bourguet J. The single-file hypothesis and the water channels induced by antidiuretic hormone. J. Membrane Biol. 1983;71(3):189–193. doi: 10.1007/BF01875460. [DOI] [PubMed] [Google Scholar]
  20. Pisano M.M., Chepelinsky A.B. Genomic cloning, complete nucleotide sequence, and structure of the human gene encoding the major intrinsic protein (MIP) of the lens. Genomics. 1991;11:981–990. doi: 10.1016/0888-7543(91)90023-8. [DOI] [PubMed] [Google Scholar]
  21. Preston G.M., Agre P. Isolation of the cDNA for erythrocyte integral membrane protein of 28 kilodaltons: Member of an ancient channel family. Proc. Natl. Acad. Sci. USA. 1991;88:11110–11114. doi: 10.1073/pnas.88.24.11110. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Preston G.M., Carroll T.P., Guggino W.B., Agre P. Appearance of water channels in Xenopus oocytes expressing red cell CHIP28 protein. Science. 1992;256:385–387. doi: 10.1126/science.256.5055.385. [DOI] [PubMed] [Google Scholar]
  23. Preston G.M., Jung J.S., Guggino W.B., Agre P. The mercury-sensitive residue at cysteine 189 in the CHIP28 water channel. J. Biol. Chem. 1993;268:17–20. [PubMed] [Google Scholar]
  24. Preston G.M., Jung J.S., Guggino W.B., Agre P. Membrane topology of aquaporin CHIP. Analysis of functional epitope-scanning mutants by vectorial proteolysis. J. Biol. Chem. 1994;269:1668–1673. [PubMed] [Google Scholar]
  25. Prevelige P., Fasman G.D. In: Prediction of protein structure and the principles of protein conformation. Fasman G.D., editor. New York, London: Plenum; 1989. pp. 391–416. [Google Scholar]
  26. Radding W. Proposed partial beta-structures for lac permease and the Na+/H+ antiporter which use similar transport and H+ coupling mechanism. J. Theor. Biol. 1991;150:239–249. doi: 10.1016/s0022-5193(05)80335-2. [DOI] [PubMed] [Google Scholar]
  27. Rao Y., Jan L.Y., Jan Y.N. Similarity of the product of the Drosophila neurogenic gene big brain to transmembrane channel proteins. Nature. 1990;345:163–167. doi: 10.1038/345163a0. [DOI] [PubMed] [Google Scholar]
  28. Rost B., Sander C. Jury returns on structure prediction. Nature. 1992;360:540. doi: 10.1038/360540b0. [DOI] [PubMed] [Google Scholar]
  29. Sandal N.N., Marcker K.A. Soybean nodulin 26 is homologous to the major intrinsic protein of the bovine lens fiber membrane. Nucl. Acids Res. 1988;16:9347. doi: 10.1093/nar/16.19.9347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Solomon A.K. Characterization of biological membranes by equivalent pores. J. Gen. Physiol. 1968;51:335–364. [PMC free article] [PubMed] [Google Scholar]
  31. Van Hoek A.N., Verkman A.S. Functional reconstitution of the isolated erythrocyte water channel CHIP28. J. Biol. Chem. 1992;267:18267–18269. [PubMed] [Google Scholar]
  32. Van Hoek A.N., Wiener M., Bicknese S., Miercke L., Biwersi J., Verkman A.S. Secondary structure analysis of purified functional CHIP28 water channels by CD and FTIR spectroscopy. Biochemistry. 1993;32(44):11847–11856. doi: 10.1021/bi00095a013. [DOI] [PubMed] [Google Scholar]
  33. Verkman A.S. Water channels in cell membranes. Annu. Rev. Physiol. 1992;54:97–108. doi: 10.1146/annurev.ph.54.030192.000525. [DOI] [PubMed] [Google Scholar]
  34. Welte W., Weiss M.S., Nestel U., Weckesser J., Schiltz E., Schulz G.E. Prediction of the general structure of OmpF and PhoE from the sequence and structure of porin from Rhodobacter capsulatus. Orientation of porin in the membrane. Biochim. Biophys. Acta. 1991;1080:271–274. doi: 10.1016/0167-4838(91)90013-p. [DOI] [PubMed] [Google Scholar]
  35. Whittembury G., Echevarría M., Gutierrez A., Gonzalez E. Contraluminal cell membrane water channels in PST exclude urea and acetamide but are formamide permeable. J. Am. Soc. Nephrol. 1991;2:729. [Google Scholar]
  36. Zhang R., Skach W., Hasegawa H., Van Hoek A.N., Verkman A.S. Cloning, functional analysis and cell localization of a kidney proximal tubule water transporter homologous to CHIP28. J. Cell Biol. 1993;120:359–369. doi: 10.1083/jcb.120.2.359. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Zhang R., van-Hoek A.N., Biwersi J., Verkman A.S. A point mutation at cysteine 189 blocks the water permeability of rat kidney water channel CHIP28k. Biochemistry. 1993;32:2938–2941. doi: 10.1021/bi00063a002. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Membrane Biology are provided here courtesy of Nature Publishing Group

RESOURCES