Riding the wave: structural and energetic principles of helical membrane proteins.

Genome sequencing efforts have revealed that perhaps as many as 20-40% of open reading frames in complex organisms may encode proteins containing at least one helical transmembrane segment. Contrasting with this approaching tidal wave of helical membrane proteins is the fact that our understanding of the sequence-structure-function relationships for membrane proteins lags far behind that of soluble proteins. This looming reality emphasizes the tremendous biochemical and structural work that remains to be done on helical membrane proteins in order to elucidate the structural and energetic principles that specify and stabilize their folds, which define their functions. These facts are not lost on the pharmaceutical industry, where successful therapeutics and major discovery efforts are targeting membrane proteins.

[1]  D. D. Thomas,et al.  Co-reconstitution of Phospholamban Mutants with the Ca-ATPase Reveals Dependence of Inhibitory Function on Phospholamban Structure* , 1999, The Journal of Biological Chemistry.

[2]  A. Engel,et al.  Two-dimensional crystallization of Escherichia coli lactose permease. , 1999, Journal of structural biology.

[3]  D. Engelman,et al.  TOXCAT: a measure of transmembrane helix association in a biological membrane. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[4]  G. Vriend,et al.  G protein-coupled receptors in silico , 1998, Journal of Molecular Medicine.

[5]  D. Bergsma,et al.  Orphan G protein-coupled receptors: a neglected opportunity for pioneer drug discovery. , 1997, Trends in pharmacological sciences.

[6]  Y. Kagawa,et al.  A purified alanine carrier composed of a single polypeptide from thermophilic bacterium PS3 driven by either proton or sodium ion gradient. , 1984, Journal of Biological Chemistry.

[7]  G. Heijne,et al.  Genome‐wide analysis of integral membrane proteins from eubacterial, archaean, and eukaryotic organisms , 1998, Protein science : a publication of the Protein Society.

[8]  J. Lee,et al.  Toward the bilayer proteome, electrospray ionization-mass spectrometry of large, intact transmembrane proteins. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[9]  H Luecke,et al.  Structure of bacteriorhodopsin at 1.55 A resolution. , 1999, Journal of molecular biology.

[10]  C. Tate,et al.  Molecular Chaperones Stimulate the Functional Expression of the Cocaine-sensitive Serotonin Transporter* , 1999, The Journal of Biological Chemistry.

[11]  D. D. Thomas,et al.  A fluorescence energy transfer method for analyzing protein oligomeric structure: application to phospholamban. , 1999, Biophysical journal.

[12]  T. Laue,et al.  Modern applications of analytical ultracentrifugation. , 1999, Annual review of biophysics and biomolecular structure.

[13]  H Luecke,et al.  Structural changes in bacteriorhodopsin during ion transport at 2 angstrom resolution. , 1999, Science.

[14]  E. Landau,et al.  Detergent‐free membrane protein crystallization , 1999, FEBS letters.

[15]  Y. Jan,et al.  Transmembrane Structure of an Inwardly Rectifying Potassium Channel , 1999, Cell.

[16]  B. Chait,et al.  The structure of the potassium channel: molecular basis of K+ conduction and selectivity. , 1998, Science.

[17]  J. Chambers,et al.  Orphan G‐protein‐coupled receptors: the next generation of drug targets? , 1998, British journal of pharmacology.

[18]  J. Bowie,et al.  Changing single side-chains can greatly enhance the resistance of a membrane protein to irreversible inactivation. , 1999, Journal of molecular biology.

[19]  C. Tate,et al.  Heterologous expression of G-protein-coupled receptors. , 1996, Trends in biotechnology.

[20]  C Menzel,et al.  Protein, lipid and water organization in bacteriorhodopsin crystals: a molecular view of the purple membrane at 1.9 A resolution. , 1999, Structure.

[21]  D. D. Thomas,et al.  Cysteine reactivity and oligomeric structures of phospholamban and its mutants. , 1998, Biochemistry.

[22]  S. White,et al.  Membrane protein folding and stability: physical principles. , 1999, Annual review of biophysics and biomolecular structure.

[23]  E. Gouaux,et al.  Overexpression of a glutamate receptor (GluR2) ligand binding domain in Escherichia coli: application of a novel protein folding screen. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[24]  D. Engelman,et al.  Membrane protein folding and oligomerization: the two-stage model. , 1990, Biochemistry.

[25]  J. Walker,et al.  Analysis of hydrophobic proteins and peptides by electrospray ionization MS. , 1996, Biochemical Society transactions.

[26]  C. Tribet,et al.  Amphipols: polymers that keep membrane proteins soluble in aqueous solutions. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[27]  H. Fritz,et al.  Dimerisation of the glycophorin A transmembrane segment in membranes probed with the ToxR transcription activator. , 1996, Journal of molecular biology.

[28]  D. D. Thomas,et al.  Depolymerization of phospholamban in the presence of calcium pump: a fluorescence energy transfer study. , 1999, Biochemistry.

[29]  W. Hubbell,et al.  Recent advances in site-directed spin labeling of proteins. , 1998, Current opinion in structural biology.

[30]  Eric Gouaux,et al.  A new protein folding screen: Application to the ligand binding domains of a glutamate and kainate receptor and to lysozyme and carbonic anhydrase , 1999, Protein science : a publication of the Protein Society.

[31]  D. Engelman,et al.  The effect of point mutations on the free energy of transmembrane alpha-helix dimerization. , 1997, Journal of molecular biology.

[32]  H. Michel,et al.  Crystallization of membrane proteins. , 1983, Current opinion in structural biology.

[33]  D C Rees,et al.  Structure of the MscL homolog from Mycobacterium tuberculosis: a gated mechanosensitive ion channel. , 1998, Science.

[34]  M. Pausch,et al.  G-protein-coupled receptors in Saccharomyces cerevisiae: high-throughput screening assays for drug discovery. , 1997, Trends in biotechnology.

[35]  D. Rees,et al.  Structure of the Escherichia coli fumarate reductase respiratory complex. , 1999, Science.

[36]  G. Rummel,et al.  Lipidic Cubic Phases: New Matrices for the Three-Dimensional Crystallization of Membrane Proteins. , 1998, Journal of structural biology.

[37]  E. Gouaux.  It's not just a phase: crystallization and X-ray structure determination of bacteriorhodopsin in lipidic cubic phases. , 1998, Structure.