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Membrane Protein Structure and Stability: Implications of the First Crystallographic Analyses

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Membrane Protein Structure

Part of the book series: Methods in Physiology Series ((METHPHYS))

Abstract

Beyond their diverse and essential biological functions, membrane proteins provide an important opportunity for examining the structural and energetic basis of protein folding and stability. In contrast to water-soluble proteins, the tertiary structures of integral membrane proteins are adopted in the predominantly nonaqueous and apolar environment of the lipid bilayer. Consequently, hydrophobic interactions, believed to contribute substantially to the stability of water-soluble proteins (Kauz-mann, 1959; Tanford, 1980; Dill, 1990a), should play a less significant role in the stabilization of integral membrane proteins (Engelman, 1982). Nevertheless, membrane proteins do adopt stable tertiary structures and maintain their biological functions under the same cellular growth conditions as water-soluble proteins. To rationalize the apparent contradiction that membrane proteins can fold stably despite the diminished significance of hydrophobic interactions, speculation has arisen that “there is something basically different about how membrane proteins fold relative to most other proteins” (Zubay, 1983). This chapter will survey the structural characteristics of membrane proteins of known three-dimensional structures, with emphasis on a comparison of general structural features observed in both water-soluble and membrane proteins. The purpose of this comparison is to assess whether membrane proteins and water-soluble proteins actually do exhibit fundamentally different types of structural organization. As the following discussion indicates, it appears that this is not the case. Despite the difference in polarity of the surrounding environment, membrane proteins and water-soluble proteins seem to represent variations on common structural themes, differing primarily in the polarity of the residues on the protein surface (Rees et al., 1989a,b).

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Reference

  • Allen, J. P., Feher, G., Yeates, T. O., Komiya, H., and Rees, D. C. (1987a) Structure of the reaction center from Rhodopseudomonas sphaeroides R-26: the protein subunits. Proc. Natl. Acad. Sci. USA 84: 6162-6166.

    Google Scholar 

  • Allen, J. P., Feher, G., Yeates, T. O., Komiya, H., and Rees, D. C. (1987b) Structure of the reaction center from Rhodopseudomonas sphaeroides R-26: the cofactors. Proc. Natl. Acad. Sci. USA 84: 5730 - 5734.

    Article  PubMed  CAS  Google Scholar 

  • Allen, J. P., Feher, G., Yeates, T. O., Komiya, H., and Rees, D. C. (1988) Structure of the reaction center from Rhodopseudomonas sphaeroides R-26: protein-cofactor (quinones and Fee+) interactions. Proc. Natl. Acad. Sci. USA 85: 8487 - 8491.

    Article  PubMed  CAS  Google Scholar 

  • Allen, J. P., Feher, G., Yeates, T. O., Rees, D. C., Deisenhofer, J., Michel, H., and Huber, R. (1986) Structural homology of reaction centers from Rhodopseudomonas sphaeroides and Rhodopseudomonas vi rid is as determined by x-ray diffraction. Proc. Natl. Acad. Sci. USA 83: 8589-8593.

    Google Scholar 

  • Baldwin, R. L. (1986) emperature dependence of the hydrophobic interaction in protein folding. Proc. Natl. Acad. Sci. USA 83: 8069-8072.

    Google Scholar 

  • Becktel, W. J., and Schellman, J. A. (1987) Protein stability curves. Biopolymers 26: 1859-1877. Berkovitch-Yellin, Z. (1985) Toward an ab initio derivation of crystal morphology. J. Am. Chem. Soc. 107: 8239 - 8253.

    Google Scholar 

  • Brouillette, C. G., McMichens, R. B., Stern, L. J., and Khorana, H. G. (1989) Structure and thermal stability of monomeric bacteriorhodpsin in mixed phospholipid/detergent micelles. Proteins Struct. Funct. Gen. 5: 38-46.

    Google Scholar 

  • Brouillette, C. G., Muccio, D. D., and Finney, T. K. (1987) pH dependence of bacteriorhodpsin thermal unfolding. Biochemistry 26: 7431 - 7438.

    Google Scholar 

  • Bryant, J. A., Knobler, C. B., and Cram, D. J. (1990) Organic molecules dimerize with high structural recognition when each possesses a large lipophilic surface containing two preorganized and complementary host and guest regions. J. Am. Chem. Soc. 112: 1254 - 1255.

    Article  CAS  Google Scholar 

  • Burres, N., and Dunker, A. K. (1980) Membrane transport through a-helical bundles. IV. Preliminary model building investigation of helix-helix interactions. J. Theor. Biol. 87: 723 - 736.

    Article  PubMed  CAS  Google Scholar 

  • Chang, C.-H., El-Kabbani, O., Tiede, D., Norris, J., and Schiffer, M. (1991) Structure of the membrane-bound protein photosynthetic reaction center from Rhodobacter sphaeroides. Biochemistry 30: 5352 - 5360.

    Article  CAS  Google Scholar 

  • Chang, C.-H., Tiede, D., Tang, J., Smith, U., Norris, J. R., and Schiffer, M. (1986) Structure of Rhodopseudomonas sphaeroides R-26 reaction center. FEBS Lett. 205: 82-86.

    Google Scholar 

  • Chothia, C. (1974) Hydrophobic bonding and accessible surface area in proteins. Nature 248: 338-339. Chothia, C., and Lesk, A. M. (1986) The relation between the divergence of sequence and structure in proteins. EMBO J. 5: 823 - 826.

    Google Scholar 

  • Chothia, C., Levitt, M., and Richardson, D. (1981) Helix to helix packing in proteins. J. Mol. Biol. 145: 215 - 250.

    Article  PubMed  CAS  Google Scholar 

  • Cowan, S. W., Schirmer, T., Rummel, G., Steiert, M., Ghosh, R., Pauptit, R. A., Jansonius, J. N., and Rosenbusch, J. P. (1992) Crystal structures explain functional properties of two E. coli porins. Nature 358: 727-733.

    Google Scholar 

  • Crick, F.H.C. (1953) The packing of a-helices: simple coiled-coils. Acta Crystallogr. 6: 689 - 697.

    Article  CAS  Google Scholar 

  • Day, M. W., Hsu, B. T., Joshua-Tor, L., Park, J.-B., Zhou, Z. H., Adams, M.W.W., and Rees, D. C. (1992) X-ray crystal structures of the oxidized and reduced forms of the rubredoxin from the marine hyperthermophilic archaebacterium Pyrococcus furiosus. Protein Sci. 1: 1494 - 1507.

    Article  CAS  Google Scholar 

  • Deisenhofer, J., Epp, O., Miki, K., Huber, R., and Michel, H. (1984) X-ray structure analysis of a membrane-protein complex: electron-density map at 3 A resolution and a model of the chromophores of the photosynthetic reaction center from Rhodopseudomonas viridis. J. Mol. Biol. 180: 385 - 398.

    Article  CAS  Google Scholar 

  • Deisenhofer, J., Epp, O., Miki, K., Huber, R., and Michel, H. (1985) Structure of the protein subunits in the photosynthetic reaction center of Rhodopseudomonas viridis at 3 A resolution. Nature 318: 618 - 624.

    Article  PubMed  CAS  Google Scholar 

  • Deisenhofer, J., and Michel, H. (1989) The photosynthetic reaction center from the purple bacterium Rhodopseudomonas viridis. EMBO J. 8: 2149 - 2170.

    CAS  Google Scholar 

  • Dill, K. A. (1990a) Dominant forces in protein folding. Biochemistry 29: 7133 - 7155.

    Article  PubMed  CAS  Google Scholar 

  • Dill, K. A. (1990b) The meaning of hydrophobicity. Science 250: 297.

    Article  PubMed  CAS  Google Scholar 

  • Ealick, S. E., Cook, W. J., Vijay-Kumar, S, Carson, M., Nagabhushan, T. L., Trotta, P. P., and Bugg, C. E. (1991) Three-dimensional structure of recombinant human interferon-y. Science 252: 698702.

    Google Scholar 

  • Eisenberg, D. (1984) Three-dimensional structure of membrane and surface proteins. Annu. Rev. Biochem. 53: 595 - 623.

    Article  PubMed  CAS  Google Scholar 

  • Eisenberg, D., and McLachlan, A. D. (1986) Solvation energy in protein folding and binding. Nature 319: 199 - 203.

    Article  PubMed  CAS  Google Scholar 

  • Eisenberg, D., Weiss, R. M., Terwilliger, T. C., and Wilcox, W. (1982) Hydrophobic moments and protein structure. Faraday Symp. Chem. Soc. 17: 109 - 120.

    Article  Google Scholar 

  • Engelman, D. M. (1982) An implication of the structure of bacteriorhodopsin: globular membrane proteins are stabilized by polar interactions. Biophys. J. 37: 187 - 188.

    Article  PubMed  CAS  Google Scholar 

  • Engelman, D. M., Henderson, R., McLachlan, A. D., and Wallace, B. A. (1980) Path of the polypeptide in bacteriorhodopsin. Proc. Natl. Acad. Sci. USA 77: 2023 - 2027.

    Article  PubMed  CAS  Google Scholar 

  • Engelman, D. M., Steitz, T. A., and Goldman, A. (1986) Identifying nonpolar transbilayer helices in amino-acid sequences of membrane-proteins. Annu. Rev. Biophys. Biophys. Chem. 15: 21 - 353.

    Article  Google Scholar 

  • Engelman, D. M., and Zaccai, G. (1980) Bacteriorhodopsin is an inside-out protein. Proc. Natl. Acad.Sci. USA 77: 5894 - 5898.

    Article  PubMed  CAS  Google Scholar 

  • Feher, G., Allen, J. P., Okamura, M. Y., and Rees, D. C. (1989) Structure and function of bacterial photosynthetic reaction centres. Nature 339: 111 - 116.

    Article  CAS  Google Scholar 

  • Gibbs, J. W. (1928) Collected Works of J. W. Gibbs. New York: Longmans.

    Google Scholar 

  • Guy, H. R., and Seetharamulu, P. (1986) Molecular model of the action potential sodium channel. Proc. Natl. Acad. Sci. U.S.A. 83: 508 - 512.

    Article  PubMed  CAS  Google Scholar 

  • Henderson, R., Baldwin, J. M., Ceska, T. A., Zemlin, F., Beckmann, E., and Downing, K. H. (1990) Model for the structure of bacteriorhodopsin based on high-resolution electron cryomicroscopy. J. Mol. Biol. 213: 899 - 929.

    Article  PubMed  CAS  Google Scholar 

  • Henderson, R., and Unwin, P.N.T. (1975) Three-dimensional model of purple membrane obtained by electron microscopy. Nature 257: 28 - 32.

    Article  PubMed  CAS  Google Scholar 

  • Huber, R., Romisch, J., and Paques, E. P. (1990) The crystal and molecular structure of human annexinV, an anticoagulant protein that binds to calcium and membranes. EMBO J. 9: 3867 - 3874.

    PubMed  CAS  Google Scholar 

  • Jackson, M. B., and Sturtevant, J. M. (1978) Phase transitions of the purple membranes of Halobacterium halobium. Biochemistry 17: 911 - 915.

    Article  CAS  Google Scholar 

  • Janin, J., Miller, S., and Chothia, C. (1988) Surface, subunit interfaces and interior of oligomeric proteins. J. Mol. Biol. 204: 155 - 164.

    Article  PubMed  CAS  Google Scholar 

  • Kahn, T. W., Sturtevant, J. M., and Engelman, D. M. (1992) Thermodynamic measurements of the contributions of helix-connecting loops and of retinal to the stability of bacteriorhodopsin. Biochemistry 31: 8829 - 8839.

    Article  PubMed  CAS  Google Scholar 

  • Kauzmann, W. (1959) Some factors in the interpretation of protein denaturation. Adv. Prot. Chem. 14: 1 - 63.

    Article  CAS  Google Scholar 

  • Komiya, H., Yeates, T. O., Rees, D. C., Allen, J. P., and Feher, G. (1988) Structure of the reaction center from Rhodopseudomonas sphaeroides R-26 and 2.4.1: symmetry relations and sequence comparisons between different species. Proc. Natl. Acad. Sci. U.S.A. 85: 8487 - 8491.

    Article  PubMed  Google Scholar 

  • Kresheck, G. C., Schneider, H., and Scheraga, H. A. (1965) The effect of D20 on the thermal stability of Membrane Protein Structure and Stability 25 proteins. Thermodynamic parameters for the transfer of model compounds from H2O to D20. J. Phys. Chem. 69: 3132 - 3144.

    Article  PubMed  CAS  Google Scholar 

  • Kyte, J., and Doolittle, R. F. (1982) A simple method for displaying the hydropathiccharacter of a protein. J. Mol. Biol. 157: 105 - 132.

    Article  PubMed  CAS  Google Scholar 

  • Lenard, J., and Singer, S. J. (1966) Protein conformation in cell membrane preparations as studied by optical rotatory dispersion and circular dichroism. Proc. Nall. Acad. Sci. USA 56: 1828 - 1835.

    Article  CAS  Google Scholar 

  • Li, J., Carroll, J., and Ellar, D. J. (1991) Crystal structure of insecticidal 5-endotoxin from Bacillus thuringiensis at 2.5 A resolution. Nature 353: 815 - 821.

    Article  PubMed  CAS  Google Scholar 

  • Miller, S., Lesk, A. M., Janin, J., and Chothia, C. (1987) Interior and surface of monomeric proteins. J. Mol. Biol. 196: 641 - 656.

    Article  PubMed  CAS  Google Scholar 

  • Murphy, K. P., Privalov, P. L., and Gill, S. J. (1990) Common features of protein unfolding and dissolution of hydrophobic compounds. Science 560: 559 - 561.

    Article  Google Scholar 

  • Nabedryk, E., Garavito, R. M., and Breton, J. (1988) "The orientation of beta sheets in porin-a polarized Fourier transform infrared spectroscopic investigation. Biophys. J. 53: 671 - 676.

    Google Scholar 

  • Shea, E. K., Klemm, J. D., Kim, P. S., and Alber, T. (1991) X-ray structure of the GCN4 lecuine zipper, a two-stranded, parallel coiled coil. Science 254: 539 - 544.

    Article  Google Scholar 

  • Parker, M. W., Pattus, F., Tucker, A. D., and Tsernoglou, D. (1989) Structure of the membrane-poreforming fragment of colicin A. Nature 337: 93 - 96.

    Article  PubMed  CAS  Google Scholar 

  • Perutz, M. F., Kendrew, J. C., and Watson, H. C. (1965) Structure and function of haemoglobin. II. Some relationships between polypeptide chain configuration and amino acid sequence. J. Mol. Biol. 13: 669 - 678.

    Article  CAS  Google Scholar 

  • Popot, J.-L., and Engelman, D. M. (1990) Membrane protein folding and oligomerization: the two-stage model. Biochemistry 29: 4031 - 4037.

    Article  PubMed  CAS  Google Scholar 

  • Popot, J.-L., Gerchman, S.-E., and Engelman, D. M. (1987) Refolding of bacteriorhodopsin in lipid bilayers-a thermodynamically controlled two stage process. J. Mol. Biol. 198: 655 - 676.

    Article  PubMed  CAS  Google Scholar 

  • Privalov, P. L. (1979) Stability of proteins: small globular proteins. Adv. Prot. Chem. 33: 167-241. Privalov, P. L. (1990) Cold denaturation of proteins. Crit. Rev. Biochem. Mol. Biol. 25: 281 - 305.

    Article  Google Scholar 

  • Privalov, P. L., and Gill, S. J. (1988) Stability of protein structure and hydrophobic interaction. Adv. Prot.Chem. 39: 191 - 234.

    Article  CAS  Google Scholar 

  • Rees, D. C., DeAntonio, L., and Eisenberg, D. (1989a) Hydrophobic organization of membrane proteins. Science 245: 510 - 513.

    Article  PubMed  CAS  Google Scholar 

  • Rees, D. C., Komiya, H., Yeates, T. O., Allen J. P., and Feher, G. (989b) The bacterial photosynthetic reaction center as a model for membrane proteins. Annu. Rev. Biochem. 58: 607 - 633.

    Google Scholar 

  • Richards, F. M. (1977) Areas, volumes, packing and protein structure. Annu. Rev. Biophys. Bioeng. 6: 151 - 176.

    Article  PubMed  CAS  Google Scholar 

  • Roth, M., Lewit-Bentley, A., Michel, H., Deisenhofer, J., Huber, R., and Oesterhelt, D. (1989) Detergent structure in crystals of a bacterial photosynthetic reaction center. Nature 340: 659 - 662.

    Article  CAS  Google Scholar 

  • Singer, S. J. (1990) The structure and insertion of integral proteins in membranes. Annu. Rev. Cell Biol. 6: 247 - 296.

    Article  PubMed  CAS  Google Scholar 

  • Smith, E. L. (1967) The evolution of proteins. Harvey Lect. 62: 231 - 256.

    CAS  Google Scholar 

  • Tanford, C. (1980) The Hydrophobic Effect. 2nd Ed. New York: Wiley.

    Google Scholar 

  • Volkin, D. B., Staubli, A., Langer, R., and Klibanov, A. M. (1991) Enzyme thermoinactivation in anhydrous organic solvents. Biotech. Bioengin. 37: 843 - 853.

    Article  CAS  Google Scholar 

  • Wallach, D.F.H., and Zahler, P. H. (1966) Protein conformations in cellular membranes. Proc. Natl. Acad. Sci. U.S.A. 56: 1552 - 1559.

    Article  PubMed  CAS  Google Scholar 

  • Weber, P. C., and Salemme, F. R. (1980) Structural and functional diversity in 4-a-helical proteins. Nature 287: 82 - 84.

    Article  PubMed  CAS  Google Scholar 

  • Weiss, M. S., Abele, U., Weckesser, J., Welte, W., Schiltz, E., and Schulz, G. E. (1991) Molecular architecture and electrostatic properties of a bacterial porin. Science 254: 1627 - 1630.

    Article  PubMed  CAS  Google Scholar 

  • Weiss, M. S., Kreusch, A., Schiltz, E., Nestel, U., Welte, W., Weckesser, J., and Schulz, G. E. (1991) The structure of porin from Rhodobacter capsulatus at 1.8 A resolution. FEBS Lett. 280: 379382.

    Google Scholar 

  • Weiss, M. S., Wacker, T., Weckesser, J., Welte, W., and Schulz, G. E. (1990) The three-dimensional structure of porin from Rhodobacter capsulatus at 3 A resolution. FEBS Lett. 267: 268 - 272.

    Article  PubMed  CAS  Google Scholar 

  • Weiss, M. S., and Schulz, G. E. (1992) Structure of porin refined at 1.8A resolution. J. Mol. Biol. 227: 493 - 509.

    Article  Google Scholar 

  • Yeates, T. O., Komiya, H., Chirino, A., Rees, D. C., Allen, J. P., and Feher, G. (1988) Structure of the reaction center from Rhodopseudomonas sphaeroides R-26 and 2.4.1: protein-cofactor (bacteriochlorophyll, bacteriopheophytin, and carotenoid) interactions. Proc. Natl. Acad. Sci. U.S.A. 85: 7993 - 7997.

    Article  PubMed  CAS  Google Scholar 

  • Yeates, T. O., Komiya, H., Rees, D. C., Allen, J. P., and Feher, G. (1987) Structure of the reaction center from Rhodopseudomonas sphaeroides R-26: membrane-protein interactions. Proc. Natl. Acad. Scie. U.S.A. 84: 6438 - 6442.

    Article  CAS  Google Scholar 

  • Zipp, A., and Kauzmann, W. (1973) Pressure denaturation of myoglobin. Biochemistry 12: 4217-4228. Zubay, G. (1983) Biochemistry. 1st Ed. Reading, MA: Addison-Wesley, p. 104.

    Google Scholar 

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Authors
  1. D. C. Rees
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  2. A. J. Chirino
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  3. K.-H. Kim
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  4. H. Komiya
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Editors and Affiliations

  1. College of Medicine, Department of Physiology and Biophysics, University of California, Irvine, Irvine, California, USA

    Stephen H. White Ph.D. (Professor of Physiology and Biophysics) (Professor of Physiology and Biophysics)

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© 1994 American Physiological Society

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Rees, D.C., Chirino, A.J., Kim, KH., Komiya, H. (1994). Membrane Protein Structure and Stability: Implications of the First Crystallographic Analyses. In: White, S.H. (eds) Membrane Protein Structure. Methods in Physiology Series. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-7515-6_1

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  • DOI: https://doi.org/10.1007/978-1-4614-7515-6_1

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