1887

Abstract

Scaffold proteins are ubiquitous chaperones that bind to proteins and facilitate the physical interaction of the components of signal transduction pathways or multi-enzymic complexes. In this study, we used a biochemical approach to dissect the molecular mechanism of a membrane-associated scaffold protein, FloT, a flotillin-homologue protein that is localized in functional membrane microdomains of the bacterium . This study provides unambiguous evidence that FloT physically binds to and interacts with the membrane-bound sensor kinase KinC. This sensor kinase activates biofilm formation in in response to the presence of the self-produced signal surfactin. Furthermore, we have characterized the mechanism by which the interaction of FloT with KinC benefits the activity of KinC. Two separate and synergistic effects constitute this mechanism: first, the scaffold activity of FloT promotes more efficient self-interaction of KinC and facilitates dimerization into its active form. Second, the selective binding of FloT to KinC prevents the occurrence of unspecific aggregation between KinC and other proteins that may generate dead-end intermediates that could titrate the activity of KinC. Flotillin proteins appear to play an important role in prokaryotes in promoting effective binding of signalling proteins with their correct protein partners.

Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.000137
2015-09-01
2019-11-16
Loading full text...

Full text loading...

/deliver/fulltext/micro/161/9/1871.html?itemId=/content/journal/micro/10.1099/mic.0.000137&mimeType=html&fmt=ahah

References

  1. Babuke T. , Tikkanen R. . ( 2007;). Dissecting the molecular function of reggie/flotillin proteins. Eur J Cell Biol 86: 525–532 [CrossRef] [PubMed].
    [Google Scholar]
  2. Bach J. N. , Bramkamp M. . ( 2013;). Flotillins functionally organize the bacterial membrane. Mol Microbiol 88: 1205–1217 [CrossRef] [PubMed].
    [Google Scholar]
  3. Bach J. N. , Bramkamp M. . ( 2015;). Dissecting the molecular properties of prokaryotic flotillins. PLoS One 10: e0116750 [CrossRef] [PubMed].
    [Google Scholar]
  4. Banse A. V. , Hobbs E. C. , Losick R. . ( 2011;). Phosphorylation of Spo0A by the histidine kinase KinD requires the lipoprotein med in Bacillus subtilis . J Bacteriol 193: 3949–3955 [CrossRef] [PubMed].
    [Google Scholar]
  5. Baruah A. , Lindsey B. , Zhu Y. , Nakano M. M. . ( 2004;). Mutational analysis of the signal-sensing domain of ResE histidine kinase from Bacillus subtilis . J Bacteriol 186: 1694–1704 [CrossRef] [PubMed].
    [Google Scholar]
  6. Bashor C. J. , Helman N. C. , Yan S. , Lim W. A. . ( 2008;). Using engineered scaffold interactions to reshape MAP kinase pathway signaling dynamics. Science 319: 1539–1543 [CrossRef] [PubMed].
    [Google Scholar]
  7. Bauer M. , Pelkmans L. . ( 2006;). A new paradigm for membrane-organizing and shaping scaffolds. FEBS Lett 580: 5559–5564 [CrossRef] [PubMed].
    [Google Scholar]
  8. Bhattacharyya R. P. , Reményi A. , Good M. C. , Bashor C. J. , Falick A. M. , Lim W. A. . ( 2006;). The Ste5 scaffold allosterically modulates signaling output of the yeast mating pathway. Science 311: 822–826 [CrossRef] [PubMed].
    [Google Scholar]
  9. Bickel P. E. , Scherer P. E. , Schnitzer J. E. , Oh P. , Lisanti M. P. , Lodish H. F. . ( 1997;). Flotillin and epidermal surface antigen define a new family of caveolae-associated integral membrane proteins. J Biol Chem 272: 13793–13802 [CrossRef] [PubMed].
    [Google Scholar]
  10. Bodrikov V. , Solis G. P. , Stuermer C. A. . ( 2011;). Prion protein promotes growth cone development through reggie/flotillin-dependent N-cadherin trafficking. J Neurosci 31: 18013–18025 [CrossRef] [PubMed].
    [Google Scholar]
  11. Bramkamp M. , Lopez D. . ( 2015;). Exploring the existence of lipid rafts in bacteria. Microbiol Mol Biol Rev 79: 81–100 [CrossRef] [PubMed].
    [Google Scholar]
  12. Branda S. S. , González-Pastor J. E. , Ben-Yehuda S. , Losick R. , Kolter R. . ( 2001;). Fruiting body formation by Bacillus subtilis . Proc Natl Acad Sci U S A 98: 11621–11626 [CrossRef] [PubMed].
    [Google Scholar]
  13. Britton R. A. , Eichenberger P. , Gonzalez-Pastor J. E. , Fawcett P. , Monson R. , Losick R. , Grossman A. D. . ( 2002;). Genome-wide analysis of the stationary-phase sigma factor (sigma-H) regulon of Bacillus subtilis . J Bacteriol 184: 4881–4890 [CrossRef] [PubMed].
    [Google Scholar]
  14. Capra E. J. , Laub M. T. . ( 2012;). Evolution of two-component signal transduction systems. Annu Rev Microbiol 66: 325–347 [CrossRef] [PubMed].
    [Google Scholar]
  15. Casey J. R. , Reithmeier R. A. . ( 1993;). Detergent interaction with band 3, a model polytopic membrane protein. Biochemistry 32: 1172–1179 [CrossRef] [PubMed].
    [Google Scholar]
  16. Chapman S. A. , Asthagiri A. R. . ( 2009;). Quantitative effect of scaffold abundance on signal propagation. Mol Syst Biol 5: 313 [CrossRef] [PubMed].
    [Google Scholar]
  17. Chen T. Y. , Liu P. H. , Ruan C. T. , Chiu L. , Kung F. L. . ( 2006;). The intracellular domain of amyloid precursor protein interacts with flotillin-1, a lipid raft protein. Biochem Biophys Res Commun 342: 266–272 [CrossRef] [PubMed].
    [Google Scholar]
  18. Daley D. O. . ( 2008;). The assembly of membrane proteins into complexes. Curr Opin Struct Biol 18: 420–424 [CrossRef] [PubMed].
    [Google Scholar]
  19. DeLoache W. C. , Dueber J. E. . ( 2013;). Compartmentalizing metabolic pathways in organelles. Nat Biotechnol 31: 320–321 [CrossRef] [PubMed].
    [Google Scholar]
  20. Dempwolff F. , Möller H. M. , Graumann P. L. . ( 2012a;). Synthetic motility and cell shape defects associated with deletions of flotillin/reggie paralogs in Bacillus subtilis and interplay of these proteins with NfeD proteins. J Bacteriol 194: 4652–4661 [CrossRef] [PubMed].
    [Google Scholar]
  21. Dempwolff F. , Wischhusen H. M. , Specht M. , Graumann P. L. . ( 2012b;). The deletion of bacterial dynamin and flotillin genes results in pleiotrophic effects on cell division, cell growth and in cell shape maintenance. BMC Microbiol 12: 298 [CrossRef] [PubMed].
    [Google Scholar]
  22. Dermine J. F. , Duclos S. , Garin J. , St-Louis F. , Rea S. , Parton R. G. , Desjardins M. . ( 2001;). Flotillin-1-enriched lipid raft domains accumulate on maturing phagosomes. J Biol Chem 276: 18507–18512 [CrossRef] [PubMed].
    [Google Scholar]
  23. Devi S. N. , Vishnoi M. , Kiehler B. , Haggett L. , Fujita M. . ( 2015;). In vivo functional characterization of the transmembrane histidine kinase KinC in Bacillus subtilis . Microbiology 161: 1092–1104 [CrossRef] [PubMed].
    [Google Scholar]
  24. Dickens M. , Rogers J. S. , Cavanagh J. , Raitano A. , Xia Z. , Halpern J. R. , Greenberg M. E. , Sawyers C. L. , Davis R. J. . ( 1997;). A cytoplasmic inhibitor of the JNK signal transduction pathway. Science 277: 693–696 [CrossRef] [PubMed].
    [Google Scholar]
  25. Diekmann Y. , Pereira-Leal J. B. . ( 2013;). Evolution of intracellular compartmentalization. Biochem J 449: 319–331 [CrossRef] [PubMed].
    [Google Scholar]
  26. Donovan C. , Bramkamp M. . ( 2009;). Characterization and subcellular localization of a bacterial flotillin homologue. Microbiology 155: 1786–1799 [CrossRef] [PubMed].
    [Google Scholar]
  27. Dueber J. E. , Wu G. C. , Malmirchegini G. R. , Moon T. S. , Petzold C. J. , Ullal A. V. , Prather K. L. , Keasling J. D. . ( 2009;). Synthetic protein scaffolds provide modular control over metabolic flux. Nat Biotechnol 27: 753–759 [CrossRef] [PubMed].
    [Google Scholar]
  28. Erwin K. N. , Nakano S. , Zuber P. . ( 2005;). Sulfate-dependent repression of genes that function in organosulfur metabolism in Bacillus subtilis requires Spx. J Bacteriol 187: 4042–4049 [CrossRef] [PubMed].
    [Google Scholar]
  29. Geng H. , Zuber P. , Nakano M. M. . ( 2007;). Regulation of respiratory genes by ResD-ResE signal transduction system in Bacillus subtilis . Methods Enzymol 422: 448–464 [CrossRef] [PubMed].
    [Google Scholar]
  30. Good M. C. , Zalatan J. G. , Lim W. A. . ( 2011;). Scaffold proteins: hubs for controlling the flow of cellular information. Science 332: 680–686 [CrossRef] [PubMed].
    [Google Scholar]
  31. Goodman A. L. , Merighi M. , Hyodo M. , Ventre I. , Filloux A. , Lory S. . ( 2009;). Direct interaction between sensor kinase proteins mediates acute and chronic disease phenotypes in a bacterial pathogen. Genes Dev 23: 249–259 [CrossRef] [PubMed].
    [Google Scholar]
  32. Hattori C. , Asai M. , Onishi H. , Sasagawa N. , Hashimoto Y. , Saido T. C. , Maruyama K. , Mizutani S. , Ishiura S. . ( 2006;). BACE1 interacts with lipid raft proteins. J Neurosci Res 84: 912–917 [CrossRef] [PubMed].
    [Google Scholar]
  33. Heermann R. , Weber A. , Mayer B. , Ott M. , Hauser E. , Gabriel G. , Pirch T. , Jung K. . ( 2009;). The universal stress protein UspC scaffolds the KdpD/KdpE signaling cascade of Escherichia coli under salt stress. J Mol Biol 386: 134–148 [CrossRef] [PubMed].
    [Google Scholar]
  34. Huang X. , Decatur A. , Sorokin A. , Helmann J. D. . ( 1997;). The Bacillus subtilis sigma(X) protein is an extracytoplasmic function sigma factor contributing to survival at high temperature. J Bacteriol 179: 2915–2921 [PubMed].
    [Google Scholar]
  35. Huang X. , Fredrick K. L. , Helmann J. D. . ( 1998;). Promoter recognition by Bacillus subtilis sigmaW: autoregulation and partial overlap with the sigmaX regulon. J Bacteriol 180: 3765–3770 [PubMed].
    [Google Scholar]
  36. Huang X. , Gaballa A. , Cao M. , Helmann J. D. . ( 1999;). Identification of target promoters for the Bacillus subtilis extracytoplasmic function sigma factor, sigma W. Mol Microbiol 31: 361–371 [CrossRef] [PubMed].
    [Google Scholar]
  37. Jiang M. , Shao W. , Perego M. , Hoch J. A. . ( 2000;). Multiple histidine kinases regulate entry into stationary phase and sporulation in Bacillus subtilis . Mol Microbiol 38: 535–542 [CrossRef] [PubMed].
    [Google Scholar]
  38. Karimova G. , Pidoux J. , Ullmann A. , Ladant D. . ( 1998;). A bacterial two-hybrid system based on a reconstituted signal transduction pathway. Proc Natl Acad Sci U S A 95: 5752–5756 [CrossRef] [PubMed].
    [Google Scholar]
  39. Koch G. , Yepes A. , Förstner K. U. , Wermser C. , Stengel S. T. , Modamio J. , Ohlsen K. , Foster K. R. , Lopez D. . ( 2014;). Evolution of resistance to a last-resort antibiotic in Staphylococcus aureus via bacterial competition. Cell 158: 1060–1071 [CrossRef] [PubMed].
    [Google Scholar]
  40. Krell T. , Lacal J. , Busch A. , Silva-Jiménez H. , Guazzaroni M. E. , Ramos J. L. . ( 2010;). Bacterial sensor kinases: diversity in the recognition of environmental signals. Annu Rev Microbiol 64: 539–559 [CrossRef] [PubMed].
    [Google Scholar]
  41. Lang D. M. , Lommel S. , Jung M. , Ankerhold R. , Petrausch B. , Laessing U. , Wiechers M. F. , Plattner H. , Stuermer C. A. . ( 1998;). Identification of reggie-1 and reggie-2 as plasmamembrane-associated proteins which cocluster with activated GPI-anchored cell adhesion molecules in non-caveolar micropatches in neurons. J Neurobiol 37: 502–523 [CrossRef] [PubMed].
    [Google Scholar]
  42. Langhorst M. F. , Reuter A. , Stuermer C. A. . ( 2005;). Scaffolding microdomains and beyond: the function of reggie/flotillin proteins. Cell Mol Life Sci 62: 2228–2240 [CrossRef] [PubMed].
    [Google Scholar]
  43. Laub M. T. , Goulian M. . ( 2007;). Specificity in two-component signal transduction pathways. Annu Rev Genet 41: 121–145 [CrossRef] [PubMed].
    [Google Scholar]
  44. LeDeaux J. R. , Yu N. , Grossman A. D. . ( 1995;). Different roles for KinA, KinB, and KinC in the initiation of sporulation in Bacillus subtilis . J Bacteriol 177: 861–863 [PubMed].
    [Google Scholar]
  45. Lee Y. H. , Kingston A. W. , Helmann J. D. . ( 2012;). Glutamate dehydrogenase affects resistance to cell wall antibiotics in Bacillus subtilis . J Bacteriol 194: 993–1001 [CrossRef] [PubMed].
    [Google Scholar]
  46. Levchenko A. , Bruck J. , Sternberg P. W. . ( 2000;). Scaffold proteins may biphasically affect the levels of mitogen-activated protein kinase signaling and reduce its threshold properties. Proc Natl Acad Sci U S A 97: 5818–5823 [CrossRef] [PubMed].
    [Google Scholar]
  47. Li M. , Hazelbauer G. L. . ( 2011;). Core unit of chemotaxis signaling complexes. Proc Natl Acad Sci U S A 108: 9390–9395 [CrossRef] [PubMed].
    [Google Scholar]
  48. Li M. , Cha D. J. , Lai Y. , Villaruz A. E. , Sturdevant D. E. , Otto M. . ( 2007;). The antimicrobial peptide-sensing system aps of Staphylococcus aureus . Mol Microbiol 66: 1136–1147 [CrossRef] [PubMed].
    [Google Scholar]
  49. Lingwood D. , Simons K. . ( 2010;). Lipid rafts as a membrane-organizing principle. Science 327: 46–50 [CrossRef] [PubMed].
    [Google Scholar]
  50. López D. , Kolter R. . ( 2010a;). Extracellular signals that define distinct and coexisting cell fates in Bacillus subtilis . FEMS Microbiol Rev 34: 134–149 [CrossRef] [PubMed].
    [Google Scholar]
  51. López D. , Kolter R. . ( 2010b;). Functional microdomains in bacterial membranes. Genes Dev 24: 1893–1902 [CrossRef] [PubMed].
    [Google Scholar]
  52. López D. , Fischbach M. A. , Chu F. , Losick R. , Kolter R. . ( 2009;). Structurally diverse natural products that cause potassium leakage trigger multicellularity in Bacillus subtilis . Proc Natl Acad Sci U S A 106: 280–285 [CrossRef] [PubMed].
    [Google Scholar]
  53. López D. , Gontang E. A. , Kolter R. . ( 2010;). Potassium sensing histidine kinase in Bacillus subtilis . Methods Enzymol 471: 229–251 [CrossRef] [PubMed].
    [Google Scholar]
  54. Mann J. M. , Carabetta V. J. , Cristea I. M. , Dubnau D. . ( 2013;). Complex formation and processing of the minor transformation pilins of Bacillus subtilis . Mol Microbiol 90: 1201–1215 [CrossRef] [PubMed].
    [Google Scholar]
  55. Marin R. , Rojo J. A. , Fabelo N. , Fernandez C. E. , Diaz M. . ( 2013;). Lipid raft disarrangement as a result of neuropathological progresses: a novel strategy for early diagnosis?. Neuroscience 245: 26–39 [CrossRef] [PubMed].
    [Google Scholar]
  56. McLoon A. L. , Kolodkin-Gal I. , Rubinstein S. M. , Kolter R. , Losick R. . ( 2011;). Spatial regulation of histidine kinases governing biofilm formation in Bacillus subtilis . J Bacteriol 193: 679–685 [CrossRef] [PubMed].
    [Google Scholar]
  57. Michel V. , Bakovic M. . ( 2007;). Lipid rafts in health and disease. Biol Cell 99: 129–140 [CrossRef] [PubMed].
    [Google Scholar]
  58. Mielich-Süss B. , Schneider J. , Lopez D. . ( 2013;). Overproduction of flotillin influences cell differentiation and shape in Bacillus subtilis . MBio 4: e00719–e00713 [CrossRef] [PubMed].
    [Google Scholar]
  59. Milano S. K. , Pace H. C. , Kim Y. M. , Brenner C. , Benovic J. L. . ( 2002;). Scaffolding functions of arrestin-2 revealed by crystal structure and mutagenesis. Biochemistry 41: 3321–3328 [CrossRef] [PubMed].
    [Google Scholar]
  60. Miller J. H. . ( 1972;). Experiments in Molecular Genetics Cold Spring Harbor. NY: Cold Spring Harbor Laboratories;.
    [Google Scholar]
  61. Morrow I. C. , Parton R. G. . ( 2005;). Flotillins and the PHB domain protein family: rafts, worms and anaesthetics. Traffic 6: 725–740 [CrossRef] [PubMed].
    [Google Scholar]
  62. Nakano M. M. , Zhu Y. . ( 2001;). Involvement of ResE phosphatase activity in down-regulation of ResD-controlled genes in Bacillus subtilis during aerobic growth. J Bacteriol 183: 1938–1944 [CrossRef] [PubMed].
    [Google Scholar]
  63. Nakano M. M. , Zuber P. , Glaser P. , Danchin A. , Hulett F. M. . ( 1996;). Two-component regulatory proteins ResD-ResE are required for transcriptional activation of fnr upon oxygen limitation in Bacillus subtilis . J Bacteriol 178: 3796–3802 [PubMed].
    [Google Scholar]
  64. Nakano M. M. , Zhu Y. , Haga K. , Yoshikawa H. , Sonenshein A. L. , Zuber P. . ( 1999;). A mutation in the 3-phosphoglycerate kinase gene allows anaerobic growth of Bacillus subtilis in the absence of ResE kinase. J Bacteriol 181: 7087–7097 [PubMed].
    [Google Scholar]
  65. Nakano S. , Küster-Schöck E. , Grossman A. D. , Zuber P. . ( 2003;). Spx-dependent global transcriptional control is induced by thiol-specific oxidative stress in Bacillus subtilis . Proc Natl Acad Sci U S A 100: 13603–13608 [CrossRef] [PubMed].
    [Google Scholar]
  66. Otto G. P. , Nichols B. J. . ( 2011;). The roles of flotillin microdomains—endocytosis and beyond. J Cell Sci 124: 3933–3940 [CrossRef] [PubMed].
    [Google Scholar]
  67. Park S. H. , Zarrinpar A. , Lim W. A. , Rewiring M. A. P. . ( 2003;). kinase pathways using alternative scaffold assembly mechanisms. Science 299: 1061–1064 [CrossRef] [PubMed].
    [Google Scholar]
  68. Reusch R. N. , Hiske T. W. , Sadoff H. L. . ( 1986;). Poly-beta-hydroxybutyrate membrane structure and its relationship to genetic transformability in Escherichia coli . J Bacteriol 168: 553–562 [PubMed].
    [Google Scholar]
  69. Schneider A. , Rajendran L. , Honsho M. , Gralle M. , Donnert G. , Wouters F. , Hell S. W. , Simons M. . ( 2008;). Flotillin-dependent clustering of the amyloid precursor protein regulates its endocytosis and amyloidogenic processing in neurons. J Neurosci 28: 2874–2882 [CrossRef] [PubMed].
    [Google Scholar]
  70. Schneider J. , Klein T. , Mielich-Süss B. , Koch G. , Franke C. , Kuipers O. P. , Kovács A. T. , Sauer M. , Lopez D. . ( 2015;). Spatio-temporal remodeling of functional membrane microdomains organizes the signaling networks of a bacterium. PLoS Genet 11: e1005140 [CrossRef] [PubMed].
    [Google Scholar]
  71. Shemesh M. , Chai Y. . ( 2013;). A combination of glycerol and manganese promotes biofilm formation in Bacillus subtilis via histidine kinase KinD signaling. J Bacteriol 195: 2747–2754 [CrossRef] [PubMed].
    [Google Scholar]
  72. Silva-Rocha R. , Martínez-García E. , Calles B. , Chavarría M. , Arce-Rodríguez A. , de Las Heras A. , Páez-Espino A. D. , Durante-Rodríguez G. , Kim J. , other authors . ( 2013;). The Standard European Vector Architecture (SEVA): a coherent platform for the analysis and deployment of complex prokaryotic phenotypes. Nucleic Acids Res 41: (D1), D666–D675 [CrossRef] [PubMed].
    [Google Scholar]
  73. Simons K. , Ikonen E. . ( 1997;). Functional rafts in cell membranes. Nature 387: 569–572 [CrossRef] [PubMed].
    [Google Scholar]
  74. Stuermer C. A. . ( 2011;). Reggie/flotillin and the targeted delivery of cargo. J Neurochem 116: 708–713 [CrossRef] [PubMed].
    [Google Scholar]
  75. Stuermer C. A. , Plattner H. . ( 2005;). The ‘lipid raft’ microdomain proteins reggie-1 and reggie-2 (flotillins) are scaffolds for protein interaction and signalling. Biochem Soc Symp 72: 109–118 [PubMed].[CrossRef]
    [Google Scholar]
  76. Tavernarakis N. , Driscoll M. , Kyrpides N. C. . ( 1999;). The SPFH domain: implicated in regulating targeted protein turnover in stomatins and other membrane-associated proteins. Trends Biochem Sci 24: 425–427 [CrossRef] [PubMed].
    [Google Scholar]
  77. Underbakke E. S. , Zhu Y. , Kiessling L. L. . ( 2011;). Protein footprinting in a complex milieu: identifying the interaction surfaces of the chemotaxis adaptor protein CheW. J Mol Biol 409: 483–495 [CrossRef] [PubMed].
    [Google Scholar]
  78. Wittig I. , Schägger H. . ( 2005;). Advantages and limitations of clear-\native PAGE. Proteomics 5: 4338–4346 [CrossRef] [PubMed].
    [Google Scholar]
  79. Wittig I. , Schägger H. . ( 2008;). Features and applications of blue-native and clear-native electrophoresis. Proteomics 8: 3974–3990 [CrossRef] [PubMed].
    [Google Scholar]
  80. Wittig I. , Braun H. P. , Schägger H. . ( 2006;). Blue native PAGE. Nat Protoc 1: 418–428 [CrossRef] [PubMed].
    [Google Scholar]
  81. Yasbin R. E. , Young F. E. . ( 1974;). Transduction in Bacillus subtilis by bacteriophage SPP1. J Virol 14: 1343–1348 [PubMed].
    [Google Scholar]
  82. Yepes A. , Schneider J. , Mielich B. , Koch G. , García-Betancur J. C. , Ramamurthi K. S. , Vlamakis H. , López D. . ( 2012;). The biofilm formation defect of a Bacillus subtilis flotillin-defective mutant involves the protease FtsH. Mol Microbiol 86: 457–471 [CrossRef] [PubMed].
    [Google Scholar]
  83. Yepes A. , Koch G. , Waldvogel A. , Garcia-Betancur J. C. , Lopez D. . ( 2014;). Reconstruction of mreB expression in Staphylococcus aureus via a collection of new integrative plasmids. Appl Environ Microbiol 80: 3868–3878 [CrossRef] [PubMed].
    [Google Scholar]
  84. Zhang H. M. , Li Z. , Tsudome M. , Ito S. , Takami H. , Horikoshi K. . ( 2005;). An alkali-inducible flotillin-like protein from Bacillus halodurans C-125.Protein J . 24: 125–131 [CrossRef] [PubMed].
    [Google Scholar]
  85. Zhao F. , Zhang J. , Liu Y. S. , Li L. , He Y.L . ( 2011;). Research advances on flotillins. Virol J 8: 479 [CrossRef] [PubMed].
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/mic.0.000137
Loading
/content/journal/micro/10.1099/mic.0.000137
Loading

Data & Media loading...

Supplements

Supplementary Data



PDF
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error