Encyclopedia of Biophysics

Living Edition
| Editors: Gordon Roberts, Anthony Watts, European Biophysical Societies

Membrane Transport: Energetics and Overview

  • Peter J. F. Henderson
Living reference work entry
DOI: https://doi.org/10.1007/978-3-642-35943-9_809-1

Overview

Cells and subcellular organelles are surrounded by a lipid-protein membrane designed to retain their contents and separate biological processes from their environment to maintain homeostasis. The membranes are comprised of lipids and proteins. It is an inherent physical property of the lipids that they form a hydrophobic bilayer essentially impermeable to the vast majority of compounds, except for a few, small, electrically neutral molecules, of which oxygen and carbon dioxide are particularly important and enter/leave by simple diffusion. Nevertheless, hydrophilic nutrients have to enter the cell and waste products have to leave. Generally, for each individual type of nutrient/waste molecule, there is a membrane protein that facilitates diffusion. The high degree of specificity that each membrane transport protein (transporter) usually exhibits for a substrate is reminiscent of the nature of enzymes. In free-living single-cell species, the rate of transport of essential...

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References

  1. Abrahams JP, Leslie AGW, Lutter R, Walker JE (1994) Structure at 2.8 A resolution of F1-ATPase from bovine heart mitochondria. Nature 370:621–628CrossRefPubMedGoogle Scholar
  2. Abramson J, Smirnova I, Kasho V, Verner G, Kaback HR, Iwata S (2003) Structure and mechanism of the lactose permease of Escherichia coli. Science 301:610–615CrossRefPubMedGoogle Scholar
  3. Adelman JL, Dale AL, Zwier MC, Bhatt D, Chong LT, Zuckerman DM, Grabe M (2011) Simulations of the alternating access mechanism of the sodium symporter Mhp1. Biophys J 101:2399–2407CrossRefPubMedPubMedCentralGoogle Scholar
  4. Adelman JL et al (2016) Stochastic steps in secondary active sugar transport. Proc Natl Acad Sci U S A 113:E3960–E3966CrossRefPubMedPubMedCentralGoogle Scholar
  5. Baldwin SA, Henderson PJF (1989) Homologies between sugar transporters from eukaryotes and prokaryotes. Annu Rev Physiol 51:459–471CrossRefPubMedGoogle Scholar
  6. Bazzone A, Madej MG, Kaback HR, Fendler K (2016) pH regulation of electrogenic sugar/H+ symport in MFS sugar permeases. Plos One 11(5):e0156392CrossRefPubMedPubMedCentralGoogle Scholar
  7. Bill RM, Henderson PJF, Iwata S, Kunji ERS, Michel H, Neutze R, Newstead S, Poolman B, Tate CG, Vogel H (2011) Overcoming barriers to membrane protein structure determination. Nat Biotechnol 29:335–340CrossRefPubMedGoogle Scholar
  8. Boudker O, Verdon G (2010) Structural perspectives on secondary active transporters. Trends Pharmacol Sci 31:418–426CrossRefPubMedPubMedCentralGoogle Scholar
  9. Calabrese AN, Jackson SM, Jones LN, Beckstein O, Heinkel F, Gsponer J, Sans M, Kokkinidou M, Pearson AR, Radford SE, Ashcroft AE, Henderson PJF (2017) Topological dissection of the membrane transport protein Mhp1 derived from cysteine accessibility and mass spectrometry. Anal Chem 89:8844–8852CrossRefPubMedPubMedCentralGoogle Scholar
  10. Claxton DP, Kazmier K, Mishra S, Mchaourab HS (2015) Navigating membrane protein structure, dynamics, and energy landscapes using spin labeling and EPR spectroscopy. Methods Enzymol 564:349–387CrossRefPubMedPubMedCentralGoogle Scholar
  11. Coleman JA, Gouaux E (2018) Structural basis for recognition of diverse antidepressants by the human serotonin transporter. Nat Struct Mol Biol 25(2):170–175CrossRefPubMedPubMedCentralGoogle Scholar
  12. Coleman JA, Green EM, Gouaux E (2016) X-ray structures and mechanism of the human serotonin transporter. Nature 532(7599):334–339CrossRefPubMedPubMedCentralGoogle Scholar
  13. Dang L, Sun Y, Huang Y, Lu F, Liu Y, Gong H, Wang J, Nieng Y (2010) Structure of a fucose transporter in an outward-open conformation. Nature 467:734–738CrossRefPubMedGoogle Scholar
  14. Deng D, Xu C, Sun P, Wu J, Yan C, Hu M, Yan N (2014) Crystal structure of the human glucose transporter GLUT1. Nature 510(7503):121CrossRefPubMedGoogle Scholar
  15. Drew D, Boudker O (2016) Shared molecular mechanisms of membrane transporters. Annu Rev Biochem 85:543–572CrossRefPubMedGoogle Scholar
  16. Elbourne LDH, Tetu S, Hassan PIT (2017) TransportDB 2.0: a database for exploring membrane transporters in sequenced genomes from all domains of life. Nucleic Acids Res.  https://doi.org/10.1093/nar/gkw1068
  17. Ethayathulla AS, Yousef MS, Amin A, Leblanc G, Kaback HR, Guan L (2014) Structure-based mechanism for Na+/melibiose symport by MelB. Nat Commun 5:3009.  https://doi.org/10.1038/ncomms4009CrossRefPubMedPubMedCentralGoogle Scholar
  18. Griffith JK, Sansom CE (eds) (1998) The transporter facts book. Academic, LondonGoogle Scholar
  19. Hediger MA, Romero MF, Peng J-B, Rolfs A, Takanaga H, Bruford EA (2004) The ABCs of solute carriers: physiological, pathological and therapeutic implications of human membrane transport proteins. Pflugers Arch 447:465–468CrossRefPubMedGoogle Scholar
  20. Heller KB, Lin EC, Wilson TH (1980) Substrate specificity and transport properties of the glycerol facilitator of Escherichia coli. J Bacteriol 144:274–278PubMedPubMedCentralGoogle Scholar
  21. Henderson PJF (1990) Proton-linked sugar transport systems in bacteria. J Bioenerg Biomembr 22:525–556CrossRefPubMedGoogle Scholar
  22. Henderson PJF (1993) The 12-transmembrane helix transporters. Curr Opin Cell Biol 5:708–721CrossRefPubMedGoogle Scholar
  23. Henderson PJF, Baldwin SA (2013) This is about the in and the out. Nat Struct Mol Biol 20:654–655CrossRefPubMedGoogle Scholar
  24. Henderson PJF, Maiden MCJ (1990) Homologous sugar transport proteins in Escherichia coli and their relatives in both prokaryotes and eukaryotes. Philos Trans R Soc Lond B 326:391–410CrossRefGoogle Scholar
  25. Hirai T, Subramaniam S (2004) Structure and transport mechanism of the bacterial oxalate transporter OxlT. Biophys J 87:3600–3607CrossRefPubMedPubMedCentralGoogle Scholar
  26. Huang Y, Lemieux MJ, Song J, Auer M, Wang DN (2003) Structure and mechanism of the glycerol-3-phosphate transporter from Escherichia coli. Science 301:616–620CrossRefPubMedGoogle Scholar
  27. Hunte C, Screpanti E, Venturi M, Rimon A, Padan E, Michel H (2005) Structure of a Na+/H+ antiporter and insights into mechanism of action and regulation by pH. Nature 435:1197–1202CrossRefPubMedGoogle Scholar
  28. Iancu CV, Zamoon J, Woo SB, Aleshin A, Choe JY (2013) Crystal structure of a glucose/H+ symporter and its mechanism of action. Proc Natl Acad Sci U S A 110:17862–17867CrossRefPubMedPubMedCentralGoogle Scholar
  29. Jardetsky O (1966) Simple allosteric model for membrane pumps. Nature 211:969–970CrossRefGoogle Scholar
  30. Kaback HR, Smirnova I, Kasho V, Nie Y, Zhou Y (2011) The alternating access transport mechanism in LacY. J Membr Biol 239:85–93CrossRefPubMedGoogle Scholar
  31. Kaplan JH (2002) Biochemistry of Na K-ATPase. Annu Rev Biochem 71:511–535CrossRefPubMedGoogle Scholar
  32. Kapoor K et al (2016) Mechanism of inhibition of human glucose transporter GLUT1 is conserved between cytochalasin B and phenylalanine amides. Proc Natl Acad Sci U S A 113:4711–4716CrossRefPubMedPubMedCentralGoogle Scholar
  33. Kazmier K, Sharma S, Islam SM, Roux B, Mchaourab HS (2014a) Conformational cycle and ion coupling mechanism of the Na+/hydantoin transporter Mhp1. Proc Natl Acad Sci U S A 111:14752–14757CrossRefPubMedPubMedCentralGoogle Scholar
  34. Kazmier K et al (2014b) Conformational dynamics of ligand-dependent alternating access in LeuT. Nat Struct Mol Biol 21(5):472–479CrossRefPubMedPubMedCentralGoogle Scholar
  35. Kazmier K, Claxton DP, Mchaourab HS (2017) Alternating access mechanisms of LeuT- fold transporters: trailblazing towards the promised energy landscapes. Curr Opin Struct Biol 45:100–108CrossRefPubMedGoogle Scholar
  36. Kodan A et al (2014) Structural basis for gating mechanisms of a eukaryotic P-glycoprotein homolog. Proc Natl Acad Sci U S A 111:4049–4054CrossRefPubMedPubMedCentralGoogle Scholar
  37. Kuchler K (2011) The ABC of ABCs: multidrug resistance and genetic diseases. FEBS J 278:3189CrossRefPubMedGoogle Scholar
  38. Kunji ERS (2009) The role and structure of mitochondrial carriers. FEBS Lett 564:239–244CrossRefGoogle Scholar
  39. Langton KP, Henderson PJF, Herbert RB (2005) Primary and secondary multidrug efflux proteins: a common transport mechanism? Nat Prod Rep 22:439–451CrossRefPubMedGoogle Scholar
  40. Lemieux MJ, Huang YF, Wang DN (2004) The structural basis of substrate translocation by the Escherichia coli glycerol-3-phosphate transporter; a member of the major facilitator superfamily. Curr Opin Struct Biol 14:405–412CrossRefPubMedGoogle Scholar
  41. Li N et al (2017) Structure of a pancreatic ATP-sensitive potassium channel. Cell 168(e10):101–110CrossRefPubMedGoogle Scholar
  42. Liu F, Zhang Z, Csanady L, Gadsby D, Chen J (2017) Molecular structure of the human CFTR ion channel. Cell 169:85–95CrossRefGoogle Scholar
  43. Locher K (2016) Mechanistic diversity in ATP-binding cassette (ABC) transporters. Nat Struct Mol Biol 23:487–493CrossRefPubMedGoogle Scholar
  44. Lolkema JS, Slotboom DJ (2005) Sequence and hydropathy profile analysis of two classes of secondary transporters. Mol Membr Biol 22:177–189CrossRefPubMedGoogle Scholar
  45. Madej MG, Sun L, Yan N, Kaback HR (2014) Functional architecture of MFS D-glucose transporters. Proc Nat Acad Sci U S A 111(7):719–727CrossRefGoogle Scholar
  46. Maiden MCJ, Davis EO, Baldwen SA, Moore DCM, Hendrson PJF (1987) Mammalian and bacterial sugar transport proteins are homologous. Nature 325:641–643CrossRefPubMedGoogle Scholar
  47. Mitchell P (1961) Coupling of phosphorylation to electron and hydrogen by a chemiosmotic type of mechanism. Nature 191:144–148CrossRefPubMedGoogle Scholar
  48. Mitchell P (1963) Molecule, group and electron translocation through natural membranes. Soc Symp Gen Microbiol 22:142–169Google Scholar
  49. Mitchell P (1967) Translocations through natural membranes. Adv Enzymol 29:33–85PubMedGoogle Scholar
  50. Mitchell P (1973) Performance and conservation of osmotic work by proton coupled solute porter systems. J Bioenerg 4:63–91CrossRefPubMedGoogle Scholar
  51. Mitchell P (1977) Vectorial chemiosmotic processes. Annu Rev Biochem 46:996–1005CrossRefPubMedGoogle Scholar
  52. Morth P, Pedersen PB, Toustrup-Jensen MS, Sorensen T-LM, Petersen J, Andersen JP, Vilsen B, Nissen P (2007) Crystal structure of the sodium-potassium pump. Nature 450:1043–1049CrossRefPubMedGoogle Scholar
  53. Morth JP, Pedersen BP, Buch-Pedersen MJ, Andersen JP, Vislen B, Palmgren MG, Nissen P (2011) A structural overview of the plasma membrane Na, K-ATPase and H-ATPase ion pumps. Nat Rev Mol Cell Biol 12:60–70CrossRefPubMedGoogle Scholar
  54. Mueckler M et al (1985) Sequence and structure of a human glucose transporter. Science 229:941–945CrossRefPubMedGoogle Scholar
  55. Nakashima R, Sakurai K, Yamasaki S, Nishino K, Yamaguchi A (2011) Structures of the multidrug exporter AcrB reveal a proximal multisite drug-binding pocket. Nature 480:565–569CrossRefPubMedGoogle Scholar
  56. Newstead S, Drew D, Cameron AD, Postis VLG, Xia X, Fowler PW, Ingram JC, Carpenter EP, Sansom MSP, Mcphenon MJ, Baldwin SA, Iwata S (2011) Crystal structure of a prokaryotic homologue of the mammalian oligopeptide transporter, PepT1 and PepT2. EMBO J 30:417–426CrossRefPubMedGoogle Scholar
  57. Nguyen LN, Ma D, Shui G, Wong P, Cazenave-Gassiot A et al (2014) Mfsd2a is a transporter for the essential omega-3 fatty acid docosahexaenoic acid. Nature 509:503–506CrossRefPubMedGoogle Scholar
  58. Noll A et al (2017) Crystal structure and mechanistic basis of a functional homolog of the antigen transporter TAP. Proc Natl Acad Sci U S A 114:E438–E447CrossRefPubMedPubMedCentralGoogle Scholar
  59. Nomura N et al (2015) Structure and mechanism of the mammalian fructose transporter GLUT5. Nature 526:397–403CrossRefPubMedPubMedCentralGoogle Scholar
  60. Pao SS, Paulsen IT, Saier MH Jr (1998) Major facilitator superfamily. Microbiol Mol Biol Rev 62:1–34PubMedPubMedCentralGoogle Scholar
  61. Paz A, Claxton DP, Kumar JP, Kazmier K, Bisignano P, Sharma S, Nolte SA, Liwag TM, Nayak V, Wright EM, Grabe M, Mchaourab HS, Abramson J (2018) Conformational transitions of the sodium-dependent sugar transporter, vSGLT. Proc Natl Acad Sci U S A 115(12):e2742–E2751CrossRefPubMedPubMedCentralGoogle Scholar
  62. Perez C, Koshy C, Yildiz O, Ziegler C (2012) Alternating-access mechanism in conformationally asymmetric trimers of the betaine transporter BetP. Nature 490(7418):126–130CrossRefPubMedGoogle Scholar
  63. Procko E, Megan L, O’Mara WF, Bennett D, Tieleman DP, Gaudet R (2009) The mechanism of ABC transporters: general lessons from structural and functional studies of an antigenic peptide transporter. FASEB J 23:1287–1302CrossRefPubMedGoogle Scholar
  64. Quistgaard EM, Low C, Moberg P, Tresaugues L, Nordlund P (2013) Structural basis for substrate transport in the GLUT-homology family of monosaccharide transporters. Nat Struct Mol Biol 20:766–768CrossRefPubMedGoogle Scholar
  65. Radestock S, Forrest LR (2011) The alternating-access mechanism of MFS transporters arises from inverted-topology repeats. J Mol Biol 407:698–715CrossRefPubMedGoogle Scholar
  66. Ren Q, Paulsen IT (2010) TransportDB. http://www.membranetransport.org/S. Accessed February 2012
  67. Ressl S, van Schelt ACT, Vanrhein C, Olt V, Ziegler C (2009) Molecular basis of transport and regulation in the Na+-betaine symporter Bet P. Nature 458:47–52CrossRefPubMedGoogle Scholar
  68. Saier MH Jr (2012) http://www.tcdb.org/
  69. Saier MH Jr, Tran CV, Barabote RD (2006) TCDB the transporter classification database for membrane transport protein analyses and information. Nucleic Acids Res 34:D181–D186CrossRefPubMedGoogle Scholar
  70. Scopelliti A, Font Sadurni J, Vandenberg R, Boudker O, Ryan R (2018) Structural characterisation reveals insights into substrate recognition by the glutamine transporter ASCT2/SLC1A5. Nature Commun 9:38–48Google Scholar
  71. Sharom FJ (2011) ABC transporters, Essays in biochemistry. Portland Press, LondonGoogle Scholar
  72. Shi Y (2013) Common folds and transport mechanisms of secondary active transporters. Annu Rev Biophys 42:51–72CrossRefPubMedGoogle Scholar
  73. Shimamura T, Weyand S, Beckstein O, Rutherford NG, Hadden JM, Sharples D, Sansom MSP, Iwata S, Henderson PJF, Cameron AD (2010) Molecular basis of alternating access membrane transport by the sodium-hydantoin transporter Mhp1. Science 328:470–473CrossRefPubMedPubMedCentralGoogle Scholar
  74. Shintre CA, Pike ACW, Li Q, Kim J-I, Barr AJ, Goubin S, Shrestha L, Yang J, Berridge G, Ross J et al (2013) Structures of ABCB10, a human ATP-binding cassette transporter in apo- and nucleotide-bound states. Proc Natl Acad Sci U S A 110(24):9710–9715CrossRefPubMedPubMedCentralGoogle Scholar
  75. Simmons KJ, Jackson SM, Brueckner F, Patching SG, Beckstein O, Ivanova E, Geng T, Weyand S, Drew D, Lanigan J, Sharples DJ, Sansom MS, Iwata S, Fishwick CW, Johnson AP, Cameron AD, Henderson PJ (2014) Molecular mechanism of ligand recognition by membrane transport protein, Mhp1. EMBO J 33:1831–1844CrossRefPubMedPubMedCentralGoogle Scholar
  76. Stein WD (1986) Transport and diffusion across cell membranes. Academic, OrlandoGoogle Scholar
  77. Sun L, Zeng X, Yan C, Sun X, Gong X, Rao Y, Yan N (2012) Crystal structure of a bacterial homologue of glucose transporters GLUT1–4. Nature 490(7420):361–366CrossRefPubMedGoogle Scholar
  78. Taylor NMI, Manolaridis I, Jackson SM, Kowal J, Stahlberg H, Locher KP (2017) Structure of the human multidrug transporter ABCG2. Nature 546:504–509PubMedGoogle Scholar
  79. Uzdavinys P, Coincon C, Nji E, Ndi M, Winkelman I, von Ballmoos C, Drew D (2017) Dissecting the proton transport pathway in electrogenic Na+/H+ antiporters. Proc Natl Acad Sci U S A 114(7):E1101–E1110CrossRefPubMedPubMedCentralGoogle Scholar
  80. Vastermark A, Saier MH Jr (2014) Evolutionary relationship between 5+5 and 7+7 inverted repeat folds within the amino acid-polyamine-organocation superfamily. Proteins 82:336–346CrossRefPubMedGoogle Scholar
  81. Verhalen B et al (2017) Energy transduction and alternating access of the mammalian ABC transporter P-glycoprotein. Nature 543(7647):738–741CrossRefPubMedPubMedCentralGoogle Scholar
  82. Vinothkumar KR, Henderson R (2016) Single particle electron cryomicroscopy: trends, issues and future perspective. Q Rev Biophys 49:e13,1–e1325CrossRefGoogle Scholar
  83. Watt IN, Montgomery MG, Runswick MJ, Leslie AGW, Walker JE (2010) Bioenergetic cost of making an adenosine triphosphate molecule in animal mitochondria. Proc Natl Acad Sci U S A 107:16823–16827CrossRefPubMedPubMedCentralGoogle Scholar
  84. West IC, Mitchell P (1970) Proton-coupled beta-galactoside translocation in non-metabolizing cells of Escherichia coli. Biochem Biophys Res Commun 41:655–661CrossRefPubMedGoogle Scholar
  85. West IC, Mitchell P (1974) Proton/sodium ion antiport in Escherichia coli. Biochem J 144:87–90CrossRefPubMedPubMedCentralGoogle Scholar
  86. Weyand S, Shimamura T, Yajima S, Suzuki S, Mirza O, Krusong K, Carpenter EP, Rutherford NG, Hadden JM, O’Reilly J, Ma P, Saidijam M, Patching SG, Hope RJ, Norbertczak HT, Roach PCJ, Iwata S, Henderson PJF, Cameron AD (2008) Structure and molecular mechanism of a nucleobase-cation-symport-1 family. Science 322:709–713CrossRefPubMedPubMedCentralGoogle Scholar
  87. Weyand S, Shimamura T, Beckstein O, Sansom MPS, Iwata S, Henderson PJF, Cameron AD (2011) The alternating access mechanism of transport as observed in the sodium-hydantoin transporter Mhp1. J Synchrotron Radiat 18:20–23CrossRefPubMedGoogle Scholar
  88. Widdas WF (1952) Inability of diffusion to account for placental glucose transfer in the sheep and consideration of the kinetics of a possible carrier transfer. Physiology 118:23–39CrossRefGoogle Scholar
  89. Williams KA (1999) Three-dimensional structure of the ion-coupled transport protein NhaA. Nature 403:112–115CrossRefGoogle Scholar
  90. Wisedchaisri G, Park M-S, Iadanza MG, Zheng H, Gonen T (2014) Proton-coupled sugar transport in the prototypical major facilitator superfamily protein XylE. Nature Commun 44:257–283Google Scholar
  91. Yan N (2013) Structural advances for the major facilitator superfamily (MFS) transporters. Trends Biochem Sci 38:151–159CrossRefPubMedGoogle Scholar
  92. Yan N (2015) Structural biology of the major facilitator superfamily transporters. Annu Rev Biophys 44:257–283CrossRefPubMedGoogle Scholar
  93. Yin Y, He X, Szewczyk P, Nguyen T, Chang G (2006) Structure of the multidrug transporter EmrD from Escherichia coli. Science 312:741–744CrossRefPubMedPubMedCentralGoogle Scholar
  94. Zhang Z, Chen J (2016) Atomic structure of the cystic fibrosis transmembrane conductance regulator. Cell 167:1586–1597CrossRefGoogle Scholar
  95. Zhang J-L, Zheng Q-C, Yu L-Y, Li Z-Q, Zhang H-X (2016) Effect of external electrical field on substrate transport of a secondary active transporter. J Chem Inf Model 56:1539–1546CrossRefPubMedGoogle Scholar

Copyright information

© European Biophysical Societies' Association (EBSA) 2018

Authors and Affiliations

  1. 1.Astbury Centre for Structural Molecular Biology and School of BioMedical SciencesUniversity of LeedsLeedsUK

Section editors and affiliations

  • Peter J. F. Henderson
    • 1
  1. 1.Astbury Centre for Structural Molecular Biology, Institute of Membrane and Systems BiologyUniversity of LeedsLeedsUK