DISCOVERIES (ISSN 2359-7232), 2014, July-September

CITATION: 

Jena B. Porosome in Cystic Fibrosis. Discoveries 2014, Jul-Sep; 2(3): e24. DOI: 10.15190/d.2014.16

Submitted: June 09, 2014; Revised: September 04, 2014; Accepted: September 05, 2014; Published: September 28, 2014; 

GO BACK to 2014, July-September issue 
GO BACK to DISCOVERIES

Porosome in Cystic Fibrosis

Bhanu P. Jena*

Wayne State University School of Medicine, Department of Physiology, Detroit, MI, USA  

*Correspondence to: 

Bhanu P. Jena, Ph.D., D.Sc., (dr. h.c. mult.), George E. Palade University Professor, Distinguished Professor, Department of Physiology, Wayne State University School of Medicine, Director of the NanoBioScience Institute, 540 E. Canfield, 5245 Gordon Scott Hall, Detroit, MI 48201-1928, Phone: 313-577-1532, Fax: 313-993-4177, E-mail: bjena@med.wayne.edu

Abstract

Macromolecular structures embedded in the cell plasma membrane called ‘porosomes’, are involved in the regulated fractional release of intravesicular contents from cells during secretion. Porosomes range in size from 15 nm in neurons and astrocytes to 100-180 nm in the exocrine pancreas and neuroendocrine cells. Porosomes have been isolated from a number of cells, and their morphology, composition, and functional reconstitution well documented. The 3D contour map of the assembly of proteins within the porosome complex, and its native X-ray solution structure at sub-nm resolution has also advanced. This understanding now provides a platform to address diseases that may result from secretory defects. Water and ion binding to mucin impart hydration, critical for regulating viscosity of the mucus in the airways epithelia. Appropriate viscosity is required for the movement of mucus by the underlying cilia. Hence secretion of more viscous mucus prevents its proper transport, resulting in chronic and fatal airways disease such as cystic fibrosis (CF). CF is caused by the malfunction of CF transmembrane conductance regulator (CFTR), a chloride channel transporter, resulting in viscous mucus in the airways. Studies in mice lacking functional CFTR secrete highly viscous mucous that adhered to the epithelium. Since CFTR is known to interact with the t-SNARE protein syntaxin-1A, and with the chloride channel CLC-3, which are also components of the porosome complex, the interactions between CFTR and the porosome complex in the mucin-secreting human airway epithelial cell line Calu-3 was hypothesized and tested. Results from the study demonstrate the presence of approximately 100 nm in size porosome complex composed of 34 proteins at the cell plasma membrane in Calu-3 cells, and the association of CFTR with the complex. In comparison, the nuclear pore complex measures 120 nm and is comprised of over 500 protein molecules. The involvement of CFTR in porosome-mediated mucin secretion is hypothesized, and is currently being tested.

Access full text of the manuscript here: See full text (pdf)

Acknowledgements:

References:

1. Cho SJ, Jeftinija K, Glavaski A, Jeftinija S, Jena BP, Anderson LL. Structure and dynamics of the fusion pores in live GH-secreting cells revealed using atomic force microscopy. Endocrinology 2002;143:1144-8.

2. Cho SJ, Quinn AS, Stromer MH, Dash S, Cho J, Taatjes DJ, et al. Structure and dynamics of the fusion pore in live cells. Cell Biol Int 2002;26:35-42.

3. Cho WJ, Jeremic A, Rognlien KT, Zhvania MG, Lazrishvili I, Tamar B, et al. Structure, isolation, composition and reconstitution of the neuronal fusion pore. Cell Biol Int 2004;28:699-708.

4. Cho WJ, Jeremic A, Jin H, Ren G, Jena BP. Neuronal fusion pore assembly requires membrane cholesterol. Cell Biol Int 2007;31:1301-8.

5. Jena BP, Cho SJ, Jeremic A, Stromer MH, Abu-Hamdah R. Structure and composition of the fusion pore. Biophys J 2003;84:1-7.

6. Jeremic A, Kelly M, Cho SJ, Stromer MH, Jena BP. Reconstituted fusion pore. Biophys J 2003;85:2035-43.

7. Schneider SW, Sritharan KC, Geibel JP, Oberleithner H, Jena BP. Surface dynamics in living acinar cells imaged by atomic force microscopy: Identification of plasma membrane structures involved in exocytosis. Proc Natl Acad Sci U S A 1997;94:316-21.

8. Jena BP. Molecular machinery and mechanism of cell secretion. Exp Biol Med 2005;230:307-19.

9. Jena BP. Secretion machinery at the cell plasma membrane. Curr Opin Struct Biol 2007;17:437-43.

10. Cho WJ, Ren G., Jena BP. EM 3D contour maps provide protein assembly at the nanoscale within the neuronal porosome complex. J Microscopy 2008;232:106-11.

11. Hou X, Lewis KT, Wu Q, Wang S, Chen X, Flack A, Mao G, Taatjes DJ, Su F, Jena BP.  Proteome of the porosome complex in human airways epithelia: Interaction with the cystic fibrosis transmembrane conductance regulator (CFTR). Journal of Proteomics 96: 82-91, 2014.

12. Lee J-S, Jeremic A, Shin L, Cho WJ, Chen X, Jena BP. Neuronal porosome proteome: molecular dynamics and architecture. J Proteomics 2012;75:3952-3962.

13. Guggino WB, Stanton BA. New insights into cystic fibrosis: molecular switches that regulate CFTR. Nature Rev 2006;7:426-436.

14. Schwiebert EM, Egan ME, Hwang T-H, Fulmer SB, Allen SS, Cutting GR, Guggino WB.  CFTR regulates outwardly rectifying chloride channels through an autocrine mechanism involving ATP. Cell 1995;81:1063–1073.

15. Naren AP, Nelson DJ, Xie W, Jovov B, Tousson A, Pevsner J, Bennett MK, Benos DJ, Quick MW, Kirk KL. Regulation of CFTR chloride channels by syntaxin and Munc 18 isoforms. Nature 1997;390:302-305.

16. Naren AP, Cobb B, Li C, Roy K, Nelson D, Heda GD, Liao J, Kirk KL, Sorscher EJ, Hanrahan J, Clancy JP. A macromolecular complex of β2AR, CFTR and EBP50 is regulated by protein kinase A. Proc Natl Acad Sci USA 2003;100:342-346.

17. Stutts MJ, Rossier BC, Boucher RC. Cystic fibrosis transmembrane conductance regulator inverts protein kinase A-mediated regulation of epithelial sodium channel single channel kinetics. J Biol Chem 1997;272:14037–14040.

18. Shumaker H, Amlal H, Frizzell R, Ulrich CD, Soleimani M. CFTR drives Na+–NHCO3– cotransport in pancreatic duct cells: a basis for defective HCO3–secretion in CF. Am J Physiol Cell Physiol 1999;276:C16–C25.

19. Ji HL, Chalfant ML, Jovo B, Lockhart JP, Parker SB, Fuller CM, Stanton BA, Benos DJ. The cytosolic termini of the β- and γ-ENaC subunits are involved in the functional interactions between cystic fibrosis transmembrane conductance regulator and epithelial sodium channel. J Biol Chem 2000;275:27947–27956.

20. Jiang QS, Li J, Dubroff R, Ahn YJ, Foskett JK, Engelhardt J, Kleyman TR. Epithelial sodium channels regulate cystic fibrosis transmembrane conductance regulator chloride channels in Xenopus oocytes. J Biol Chem 2000;275:13266–13274.

21. Sun F, Hug MJ, Bradbury NA, Frizzell RA. Protein kinase A associates with cystic fibrosis transmembrane conductance regulator via an interaction with ezrin. J. Biol. Chem. 2000;275:14360–14366.

22. Cheung KH, Leung CT, Leung GP, Wong PY. Synergistic effects of cystic fibrosis transmembrane conductance regulator and aquaporin-9 in the rat epididymis. Biol Reprod 2003;68:1505–1510.

23. Ganeshan R, Di A, Nelson DJ, Quick MW, Kirk KL. The interaction between syntaxin 1A and cystic fibrosis transmembrane conductance regulator Cl– channels is mechanistically distinct from syntaxin 1A–SNARE interactions. J Biol Chem 2003;278:2876–2885.

24. Ko SBH, Zeng W, Dorwart MR, Lou X, Kim KH, Millen L, Goto H, Naruse S, Soyombo A, Thomas PJ, Muallem S. Gating of CFTR by the STAS domain of SLC26 transporters. Nature Cell Biol 2004;6:343–350.

25. Li, C., Roy, K., Dandridge, K. & Naren, A. P. Molecular assembly of cystic fibrosis transmembrane conductance regulator in plasma membrane. J. Biol. Chem. 2004;279:24673–24684.

26. Yoo D, Flagg TP, Olsen O, Raghuram V, Foskett JK, Welling PA. Assembly and trafficking of a multiprotein ROMK (Kir 1.1) channel complex by PDZ interactions. J Biol Chem 2004;279:6863–6873.

27. Guggino WB. The cystic fibrosis transmembrane regulator forms macromolecular complexes with PDZ domain scaffold proteins. Proc Am Thor Soc 2004;1:28–32.

28. Riordan JR. Assembly of functional CFTR chloride channels. Annu Rev Physiol 2005;67:701–718.

29. Quinton PM. Chloride impermeability in cystic fibrosis. Nature. 1983;301:421–422.

30. Riordan JR, Rommens JM, Kerem BS, Alon N, Rozmahel R, Grzelczak Z, Zielenski J, Lok S, Plavsic N, Chou JL, Drumm ML, Iannuzzi MC, Collins FC, Tsui L-C. Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science 1989;245:1066–1073.

31. Gustafsson JK, Ermund A, Ambrot D, Johansson MEV, Nilsson HE, Thorell K, Hebert H, Sjövall H, Hansson GC. Bicarbonate and functional CFTR channel are required for proper mucin secretion and link cystic fibrosis with its mucus phenotype. ScJ Exp Med 2012;209:1263–1272.

32. Knowles MR, Boucher RC. Mucus clearance as a primary innate defense mechanism for mammalian airways. J Clin Invest 2002;109:571–577.

33. Hovenberg HW, Davies JR, Carlstedt I. Different mucins are produced by the surface epithelium and the submucosa in human trachea: identification of MUC5AC as a major mucin from the goblet cells. Biochem J 1996;318:319–324.

34. Wickstrom C, Davies JR, Eriksen GV, Veerman EC, Carlstedt I. MUC5B is a major gel-forming, oligomeric mucin from human salivary gland, respiratory tract and endocervix: identification of glycoforms and C-terminal cleavage. Biochem J 1998;334:685–93.

35. Finkelstein A, Zimmerberg J, Cohen FS. Osmotic swelling of vesicles: its role in the fusion of vesicles with planar phospholipid bilayer membranes and its possible role in exocytosis. Annu Rev Physiol 1986;48:163-174.

36. Holz RW. The role of osmotic forces in exocytosis from adrenal chromaffin cells. Annu Rev Physiol 1986;48:175-189.

37. Fernandez JM, Villalon M, Verdugo P. Reversible condensation of mast cell secretory products in vitro. Biophys J 1991;59:1022-1027.

38. Monck JR, Oberhauser AF, Alverez de Toledo G, Fernandez JM. Is swelling of the secretory granule matrix the force that dilates the exocytotic fusion pore? Biophys J 1991;59:39-47.

39. Jena BP, Schneider SW, Geibel JP, Webster P, Oberleithner H, Sritharan KC. Gi regulation of secretory vesicle swelling examined by atomic force microscopy.  Proc Natl Acad Sci USA  1997;94:13317-13322.

40. Cho S-J, Sattar AKM, Jeong E-H, Satchi M, Cho J, Dash S, Mayes MS, Stromer MH, Jena BP. Aquaporin 1 regulates GTP-induced rapid gating of water in secretory vesicles.  Proc Natl Acad Sci USA 2002;99:4720-4724.

41. Kelly M, Cho W-J, Jeremic A, Abu-Hamdah R, Jena BP. Vesicle swelling regulates content expulsion during secretion. Cell Biol Int 2004;28:709-716.

42. Kelly M, Abu-Hamdah R, Cho S-J, Ilie AL, Jena BP. Patch clamped single pancreatic zymogen granules: direct measurement of ion channel activities at the granule membrane. Pancreatology 2005;5:443-449.

43. Lee J-S, Cho W-J, Shin L, Jena BP. Involvement of cholesterol in synaptic vesicle swelling.  Exp Biol Med 2010;235:470-477.

44. Shin L, Basi N, Lee J-S, Cho W-J, Chen Z, Abu-Hamdah R, Oupicky D, Jena BP. Involvement of vH+-ATPase in synaptic vesicle swelling. J Neurosci Res 2010;88:95-101.

45. Chen Z-H, Lee, J-S, Shin L, Cho W-J, Jena BP. Involvement of β-adrenergic receptor in synaptic vesicle swelling and implication in neurotransmitter release. J Cell Mol Med 2011;15:572-576.

46. Cho S-J, Wakade A, Pappas GD, Jena BP.  New structure involved in transient membrane fusion and exocytosis. New York Acad Sci Annal 2002;971:254-256.

47. Trimble WS, Cowan DW, Scheller RH. VAMP-1: A synaptic vesicle-associated integral membrane protein. Proc Natl Acad Sci USA 85: 4538-4542, 1988.

48. Bennett MK, Calakos N, Scheller RH. Syntaxin: A synaptic protein implicated in docking of synaptic vesicles at presynaptic active zones. Science 257: 255-259, 1992.

49. Oyler GA, Higgins GA, Hart RA, Battenberg E, Billingsley M, Bloom FE, Wilson MC. The identification of a novel synaptosomal-associated protein, SNAP-25, differentially expressed by neuronal subpopulations. J Cell Biol 109: 3039-3052, 1989.

50. Weber T, Zemelman BV, McNew JA, Westerman B, Gmachi M, Parlati F, Söllner TH, Rothman JE. SNAREpins: minimal machinery for membrane fusion. Cell 92: 759-772, 1998.

51. Sutton RB, Fasshauer D, Jahn R, Brunger AT. Crystal structure of a SNARE complex involved in synaptic exocytosis at 2.4 Å resolution. Nature 395: 347–353, 1998.

52. Cho SJ, Kelly M, Rognlien KT, Cho JA, Hörber JKH, Jena BP. SNAREs in opposing bilayers interact in a circular array to form conducting pores.  Biophys J 83: 5: 2522-2527, 2002.

53. Jeremic A, Kelly M, Cho JH, Cho SJ, Hörber JKH, Jena BP. Calcium drives fusion of SNARE-apposed bilayers.  Cell Biol Int 28: 19-31, 2004.

54. Jeremic A, Cho WJ, Jena BP. Membrane fusion: what may transpire at the atomic level. J Biol Phys & Chem 4: 139-142, 2004.

55. Cho WJ, Jeremic A, Jena BP. Size of supramolecular SNARE complex: membrane-directed self-assembly.  J Am Chem Soc 127: 10156-10157, 2005.

56. Jeremic A, Quinn AS, Cho WJ, Taatjes DJ, Jena BP. Energy-dependent disassembly of self-assembled SNARE complex: observation at nanometer resolution using atomic force microscopy.  J Am Chem Soc 128: 26-27, 2006.

57. Cook JD, Cho WJ, Stemmler TL, Jena BP. Circular dichroism (CD) spectroscopy of the assembly and disassembly of SNAREs: the proteins involved in membrane fusion in cells. Chem Phys Lett 462: 6-9, 2008.

58. Shin L, Cho WJ, Cook J, Stemmler T, Jena BP. Membrane lipids influence protein complex assembly-disassembly. J Am Chem Soc 132: 5596-5597, 2010.

59. Potoff JJ, Issa Z, Manke CW Jr, Jena BP. Ca2+-Dimethylphosphate complex formation: providing insight into Ca2+ mediated local dehydration and membrane fusion in cells. Cell Biol Int 32: 361-366, 2008.

60. Cho WJ, Lee JS, Ren G, Zhang L, Shin L, Manke CW, Potoff J, Kotaria N, Zhvania MG, Jena BP. Membrane-directed molecular assembly of the neuronal SNARE complex. J Cell Mol Med 15: 31-37, 2011.

61. Misura KM, Scheller RH, Weis WI. Three-dimensional structure of the neuronal-Sec1–syntaxin 1a complex. Nature 404: 355–362, 2000.

62. Südhof TC. The synaptic vesicle cycle. Annu Rev Neurosci 27: 509–547, 2004.

63. Portis A, Newton C, Pangborn W, Papahadjopoulos D. Studies on the mechanism of membrane fusion: evidence for an intermembrane Ca2+ phospholipid complex, synergism with Mg2+, and inhibition by spectrin. Biochemistry 18: 780-790, 1979.

64. Pobbati AV, Stein A, Fasshauer D. N- to C-terminal SNARE complex assembly promotes rapid membrane fusion. Science 313: 673–676, 2006.

65. Jahn R, Scheller RH. SNAREs–engines for membrane fusion. Nature Rev Mol Cell Biol 7: 631–643, 2006.

66. Shen J, Tareste DC, Paumet F, Rothman JE, Melia TJ. Selective activation of cognate SNAREpins by Sec1/Munc18 proteins. Cell 128: 183–195, 2007.

67. Martens S, Kozlov MM, McMahon HT. How synaptotagmin promotes membrane fusion. Science 316: 1205–1208, 2007.

68. Wickner W, Schekman R. Membrane fusion. Nature Struct Mol Biol 15: 658–664, 2008.

69. Chapman ER. How does synaptotagmin trigger neurotransmitter release? Annu Rev Biochem 77: 615–641, 2008.

70. Hui E, Johnson CP, Yao J, Dunning FM, Chapman ER. Synaptotagmin-mediated bending of the target membrane is a critical step in Ca2+-regulated fusion. Cell 138: 709–721, 2009.

71. Südhof TC, Rothman JE. Membrane fusion: grappling with SNARE and SM proteins. Science 323: 474–477, 2009.

72. Stein A, Weber G, Wahl MC, Jahn R. Helical extension of the neuronal SNARE complex into the membrane. Nature 460: 525–528, 2009.

73. Brunger AT, Weninger K, Bowen M, Chu S. Single-molecule studies of the neuronal SNARE fusion machinery. Annu Rev Biochem 78: 903–928, 2009.

74. Südhof TC, Rizo J. Synaptic vesicle exocytosis. Cold Spring Harb Perspect Biol 3: a005637, 2011.

75. Yao J, Gaffaney JD, Kwon SE, Chapman ER. Doc2 is a Ca2+ sensor required for asynchronous neurotransmitter release. Cell 147: 666–677, 2011.

76. Diao J, Ishitsuka Y, Bae WR. Single-molecule FRET study of SNARE-mediated membrane fusion. Biosci Rep 31: 457–463, 2011.

77. Szklarczyk D, Franceschini A, Kuhn M, Simonovic M, Roth A, Minguez P, Doerks T, Stark M, Mueller J, Bork P, Jensen LJ, von Mering C. The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored. Nucleic Acid Res 39: D561-D568, 2011.

78. Lam AD, Tryoen-Toth P, Tsai B, Vatile N, Stuenkel EL. SNARE-catalyzed fusion events are regulated by syntaxin1A-lipid interactions.  Moll Biol Cell 19: 485–497, 2008.

79. Clifford-Nunn B, Showalter HD, Andrews PC. Quaternary diamines as mass spectrometry cleavable crosslinkers for protein interactions. Journal of the American Society for Mass Spectrometry 23:201-212, 2012.

80. Kovari, L.C., Brunzelle, J.S., Lewis, K.T., Cho, W.J., Lee, J-S., Taatjes, D.J., Jena, B.P. (2014) X-ray solution structure of the native neuronal porosome-synaptic vesicle complex: Implication in neurotransmitter release. Micron 56:37-43.

81. Szymborska A, de Marco A, Daigle N, Cordes VC, Briggs JAG, Ellenberg J. Nuclear pore scaffold structure analyzed by super-resolution microscopy and particle averaging. Science 341:655-658, 2013.

82. Gray JJ, Moughon SE, Kortemme T, Schueler-Furman O, Misura KM, Morozov AV, Baker D. Protein-protein docking predictions for the CAPRI experiment. Proteins 52:118-122, 2003.

83. Smith GR, Sternberg MJ. Prediction of protein-protein interactions by docking methods. Curr Opin Struct Biol 12:28-35, 2002.

84. Janin J, Henrick K, Moult J, Eyck LT, Sternberg MJ, Vajda S, Vakser I, Wodak SJ. CAPRI: a Critical Assessment of PRedicted Interactions. Proteins 52:2-9, 2003.

85. Schneidman-Duhovny D, Inbar Y, Polak V, Shatsky M, Halperin I, Benyamini H, Barzilai A, Dror O, Haspel N, Nussinov R, Wolfson HJ. Taking geometry to its edge: fast unbound rigid (and hinge-bent) docking. Proteins 52:107-112, 2003.

86. Katchalski-Katzir E, Shariv I, Eisenstein M, Friesem AA, Aflalo C, Vakser IA. Molecular surface recognition: determination of geometric fit between proteins and their ligands by correlation techniques. Proc Natl Acad Sci USA 89:2195-2199, 1992.

87. Gabb HA, Jackson RM, Sternberg MJ. Modelling protein docking using shape complementarity, electrostatics and biochemical information. J Mol Biol 272:106-120, 1997.

88. Moont G, Sternberg MJ. Modeling protein-protein and protein-DNA docking, edited by Lengauer T. Weinheim: Wiley-VCH, 2001.

89. Jackson RM, Gabb HA, Sternberg MJ. Rapid refinement of protein interfaces incorporating solvation: application to the docking problem. J Mol Biol 276:265-285, 1998.

90. Vakser IA. Protein docking for low-resolution structures. Protein Eng 8:371-377, 1995.

91. Mandell JG, Roberts VA, Pique ME, Kotlovyi V, Mitchell JC, Nelson E, Tsigelny I, Ten Eyck LF. Protein docking using continuum electrostatics and geometric fit. Protein Eng 14:105-113, 2001.

92. Chen R, Li L, Weng Z. ZDOCK: an initial-stage protein-docking algorithm. Proteins 52:80-87, 2003.

93. Ritchie DW, Kemp GJ. Protein docking using spherical polar Fourier correlations. Proteins 39:178-194, 2000.

94. Fernandez-Recio J, Totrov M, Abagyan R. Soft protein- protein docking in internal coordinates. Protein Sci 11:280-291, 2002.

95. Gray JJ, Moughon S, Wang C, Schueler-Furman O, Kuhlman B, Rohl CA, Baker D. Protein-protein docking with simultaneous optimization of rigid-body displacement and side-chain conformations. J Mol Biol 331:281-299, 2003.

96. Gabdoulline RR, Wade RC. Protein-protein association: investigation of factors influencing association rates by Brownian dynamics simulations. J Mol Biol 306:1139-1155, 2001.

97. Fitzjohn PW, Bates PA. Guided docking: first step to locate potential binding sites. Proteins 52:28-32, 2003.

98. Aloy P, Russell RB. Interrogating protein interaction networks through structural biology. Proc Natl Acad Sci USA 99:5896-5901, 2002.

99. Aloy P, Bottcher B, Ceulemans H, Leutwein C, Mellwig C, Fischer S, Gavin AC, Bork P, Superti-Furga G, Serrano L, Russell RB. Structure-based assembly of protein complexes in yeast. Science 303:2026-2029, 2004.

100. Pieper U, Eswar N, Braberg H, Madhusudhan MS, Davis FP, Stuart AC, Mirkovic N, Rossi A, Marti-Renom MA, Fiser A, Webb B, Greenblatt D, Huang CC, Ferrin TE, Sali A. MODBASE, a database of annotated comparative protein structure models, and associated resources. Nucleic Acids Res 32: D217-D222, 2004.

101. Marti-Renom MA, Stuart AC, Fiser A, Sanchez R, Melo F, Sali A. Comparative protein structure modeling of genes and genomes. Annu Rev Biophys Biomol Struct 29:291-325, 2000.

102. Volkmann N, Hanein D, Ouyang G, Trybus KM, DeRosier DJ, Lowey S. Evidence for cleft closure in actomyosin upon ADP release. Nat Struct Biol 7:1147-1155, 2000.

103. Roseman AM. Docking structures of domains into maps from cryo-electron microscopy using local correlation. Acta Crystallogr D Biol Crystallogr 56:1332-1340, 2000.

104. Wriggers W, Birmanns S. Using situs for flexible and rigid-body fitting of multiresolution single-molecule data. J Struct Biol 133:193-202, 2001.

105. Ceulemans H, Russell RB. Fast fitting of atomic structures to lower resolution electron density maps by surface overlap maximization. J Mol Biol 338:783-793, 2004.

106. Volkmann N, Hanein D. Quantitative fitting of atomic models into observed densities derived by electron microscopy. J Struct Biol 125:176-184, 1999.

107. Rossmann MG, Bernal R, Pletnev SV. Combining electron microscopic with x-ray crystallographic structures. J Struct Biol 136:190-200, 2001.

108. Chiu W, Baker ML, Jiang W, Zhou ZH. Deriving folds of macromolecular complexes through electron cryomicroscopy and bioinformatics approaches. Curr Opin Struct Biol 12:263-269, 2002.

GO BACK to the 2014, July-September issue
GO BACK to DISCOVERIES 
MEET OUR EDITORIAL BOARD 
SUBMIT A MANUSCRIPT

 Email us at info@discoveriesjournals.org if you have any questions.