Home LiteratureArticle Details
PMID: 20512644 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

SNARE complex zipping as a driving force in the dilation of proteinaceous fusion pores.

The Journal of membrane biology ·Vol. 235 ·No. 2 ·2010-06-00 ·Pages 89-100

Jackson MB

Abstract

The assembly of SNARE proteins into a tight complex has been hypothesized to drive membrane fusion. A model of the initial fusion pore as a proteinaceous channel formed by SNARE proteins places their membrane anchors in separate membranes. This leaves the possibility of a final assembly step that brings the membrane anchors together and drives fusion pore expansion. The present study develops a model for expansion in which the final SNARE complex zipping step drives a transition from a proteinaceous fusion pore to a lipidic fusion pore. An estimate of the energy released upon merger of the helical segments of the SNARE motifs with the helical segments of the membrane anchors indicates that completing the assembly of a few SNARE complexes can overcome the elastic energy that opposes lipid bilayer deformation into a narrow fusion pore. The angle between the helical axes of the membrane anchor and SNARE motif serves as a useful reaction coordinate for this transition. Energy was calculated as a function of this angle, incorporating contributions from membrane bending, SNARE complex assembly, membrane anchor flexing and hydrophobic interactions. The rate of this transition was evaluated as a process of diffusion over the barrier imposed by these combined energies, and the rates estimated were consistent with experimental measurements.

MeSH Terms
Animals Exocytosis/physiology Humans Lipid Bilayers/chemistry,metabolism Membrane Fusion/physiology Membrane Proteins/chemistry,metabolism Models, Biological Models, Theoretical SNARE Proteins/chemistry,metabolism
Chemicals
Lipid Bilayers Membrane Proteins SNARE Proteins
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Jackson Meyer B
Department of Physiology, University of Wisconsin, Madison, USA. mjackson@physiology.wisc.edu
References (59)
59 references, click to expand
  1. Lipid flow through fusion pores connecting membranes of different tensions.
    Biophys J. 1999 Jun;76(6):2951-65 PMID: 10354423
  2. Empirical correlation between hydrophobic free energy and aqueous cavity surface area.
    Proc Natl Acad Sci U S A. 1974 Aug;71(8):2925-7 PMID: 16578715
  3. SNARE complexes and neuroexocytosis: how many, how close?
    Trends Biochem Sci. 2005 Jul;30(7):367-72 PMID: 15935678
  4. Lipid bilayer thickness varies linearly with acyl chain length in fluid phosphatidylcholine vesicles.
    J Mol Biol. 1983 May 15;166(2):211-7 PMID: 6854644
  5. Hydrophobic association of alpha-helices, steric dewetting, and enthalpic barriers to protein folding.
    Proc Natl Acad Sci U S A. 2007 Apr 10;104(15):6206-10 PMID: 17404236
  6. Interfacial free energy and the hydrophobic effect.
    Proc Natl Acad Sci U S A. 1979 Sep;76(9):4175-6 PMID: 16592699
  7. Protein-lipid interplay in fusion and fission of biological membranes.
    Annu Rev Biochem. 2003;72:175-207 PMID: 14527322
  8. Areas, volumes, packing and protein structure.
    Annu Rev Biophys Bioeng. 1977;6:151-76 PMID: 326146
  9. Membrane bending energy and fusion pore kinetics in Ca(2+)-triggered exocytosis.
    Biophys J. 2010 Jun 2;98(11):2524-34 PMID: 20513396
  10. Recent progress in understanding hydrophobic interactions.
    Proc Natl Acad Sci U S A. 2006 Oct 24;103(43):15739-46 PMID: 17023540
  11. SNAREs--engines for membrane fusion.
    Nat Rev Mol Cell Biol. 2006 Sep;7(9):631-43 PMID: 16912714
  12. Synaptotagmin IV modulation of vesicle size and fusion pores in PC12 cells.
    Biophys J. 2010 Mar 17;98(6):968-78 PMID: 20303854
  13. Structural insights into the SNARE mechanism.
    Biochim Biophys Acta. 2003 Aug 18;1641(2-3):87-97 PMID: 12914950
  14. A quantitative model for membrane fusion based on low-energy intermediates.
    Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):7235-40 PMID: 11404463
  15. Membrane mechanics can account for fusion pore dilation in stages.
    Biophys J. 1995 Dec;69(6):2489-500 PMID: 8599655
  16. Structural transitions in the synaptic SNARE complex during Ca2+-triggered exocytosis.
    J Cell Biol. 2006 Jan 16;172(2):281-93 PMID: 16418536
  17. Hydrophobicity of amino acid residues in globular proteins.
    Science. 1985 Aug 30;229(4716):834-8 PMID: 4023714
  18. v-SNARE actions during Ca(2+)-triggered exocytosis.
    Cell. 2007 Oct 19;131(2):351-63 PMID: 17956735
  19. Transmembrane segments of syntaxin line the fusion pore of Ca2+-triggered exocytosis.
    Science. 2004 Apr 9;304(5668):289-92 PMID: 15016962
  20. Helical extension of the neuronal SNARE complex into the membrane.
    Nature. 2009 Jul 23;460(7254):525-8 PMID: 19571812
  21. How proteins produce cellular membrane curvature.
    Nat Rev Mol Cell Biol. 2006 Jan;7(1):9-19 PMID: 16365634
  22. SNARE-catalyzed fusion events are regulated by Syntaxin1A-lipid interactions.
    Mol Biol Cell. 2008 Feb;19(2):485-97 PMID: 18003982
  23. Vesicle fusion from yeast to man.
    Nature. 1994 Jul 21;370(6486):191-3 PMID: 8028665
  24. Stalk mechanism of vesicle fusion. Intermixing of aqueous contents.
    Eur Biophys J. 1989;17(3):121-9 PMID: 2792021
  25. Close is not enough: SNARE-dependent membrane fusion requires an active mechanism that transduces force to membrane anchors.
    J Cell Biol. 2000 Jul 10;150(1):105-17 PMID: 10893260
  26. Intracellular membrane fusion.
    Adv Second Messenger Phosphoprotein Res. 1994;29:81-96 PMID: 7848733
  27. The membrane-dipped neuronal SNARE complex: a site-directed spin labeling electron paramagnetic resonance study.
    Biochemistry. 2002 Jul 23;41(29):9264-8 PMID: 12119042
  28. Measured work of deformation and repulsion of lecithin bilayers.
    Proc Natl Acad Sci U S A. 1979 Jun;76(6):2750-4 PMID: 288063
  29. The role of the C terminus of the SNARE protein SNAP-25 in fusion pore opening and a model for fusion pore mechanics.
    Proc Natl Acad Sci U S A. 2008 Oct 7;105(40):15388-92 PMID: 18829435
  30. Crystal structure of a SNARE complex involved in synaptic exocytosis at 2.4 A resolution.
    Nature. 1998 Sep 24;395(6700):347-53 PMID: 9759724
  31. Single vesicle millisecond fusion kinetics reveals number of SNARE complexes optimal for fast SNARE-mediated membrane fusion.
    J Biol Chem. 2009 Nov 13;284(46):32158-66 PMID: 19759010
  32. The elasticity of alpha-helices.
    J Chem Phys. 2005 Jun 22;122(24):244912 PMID: 16035821
  33. Reconciling the magnitude of the microscopic and macroscopic hydrophobic effects.
    Science. 1991 Apr 5;252(5002):106-9 PMID: 2011744
  34. Insertion of the membrane-proximal region of the neuronal SNARE coiled coil into the membrane.
    J Biol Chem. 2003 Apr 4;278(14):12367-73 PMID: 12529381
  35. Springs and zippers: coiled coils in SNARE-mediated membrane fusion.
    Structure. 1998 Dec 15;6(12):1487-91 PMID: 9862813
  36. Electrostatic interactions between the syntaxin membrane anchor and neurotransmitter passing through the fusion pore.
    Biophys J. 2005 Mar;88(3):L20-2 PMID: 15653732
  37. Neurotransmitter release - four years of SNARE complexes.
    Curr Opin Neurobiol. 1997 Jun;7(3):310-5 PMID: 9232812
  38. Minimum membrane bending energies of fusion pores.
    J Membr Biol. 2009 Oct;231(2-3):101-15 PMID: 19865786
  39. Protease resistance of syntaxin.SNAP-25.VAMP complexes. Implications for assembly and structure.
    J Biol Chem. 1998 May 1;273(18):11370-7 PMID: 9556632
  40. Field theoretic study of bilayer membrane fusion. I. Hemifusion mechanism.
    Biophys J. 2004 Nov;87(5):3277-90 PMID: 15326031
  41. Modeling water, the hydrophobic effect, and ion solvation.
    Annu Rev Biophys Biomol Struct. 2005;34:173-99 PMID: 15869376
  42. Regulation of membrane fusion by the membrane-proximal coil of the t-SNARE during zippering of SNAREpins.
    J Cell Biol. 2002 Sep 2;158(5):929-40 PMID: 12213837
  43. Evolution of lipidic structures during model membrane fusion and the relation of this process to cell membrane fusion.
    Biochemistry. 1997 May 27;36(21):6251-9 PMID: 9174340
  44. Synaptotagmin-Ca2+ triggers two sequential steps in regulated exocytosis in rat PC12 cells: fusion pore opening and fusion pore dilation.
    J Physiol. 2006 Jan 15;570(Pt 2):295-307 PMID: 16293646
  45. The length of the flexible SNAREpin juxtamembrane region is a critical determinant of SNARE-dependent fusion.
    Mol Cell. 1999 Sep;4(3):415-21 PMID: 10518222
  46. Determination of the hydrocarbon core structure of fluid dioleoylphosphocholine (DOPC) bilayers by x-ray diffraction using specific bromination of the double-bonds: effect of hydration.
    Biophys J. 1998 May;74(5):2419-33 PMID: 9591668
  47. Energetics of protein folding.
    J Mol Biol. 2007 Aug 10;371(2):283-301 PMID: 17582437
  48. Stalk model of membrane fusion: solution of energy crisis.
    Biophys J. 2002 Feb;82(2):882-95 PMID: 11806930
  49. Activity-dependent changes in partial VAMP complexes during neurotransmitter release.
    Nat Neurosci. 1999 Dec;2(12):1078-83 PMID: 10570484
  50. Membrane fusion: stalk model revisited.
    Biophys J. 2002 Feb;82(2):693-712 PMID: 11806912
  51. Structure and function of SNARE and SNARE-interacting proteins.
    Q Rev Biophys. 2005 Feb;38(1):1-47 PMID: 16336742
  52. Three SNARE complexes cooperate to mediate membrane fusion.
    Proc Natl Acad Sci U S A. 2001 Jul 3;98(14):8065-70 PMID: 11427709
  53. Synaptotagmin arrests the SNARE complex before triggering fast, efficient membrane fusion in response to Ca2+.
    Nat Struct Mol Biol. 2008 Aug;15(8):827-35 PMID: 18622390
  54. Dynamics of fusion pores connecting membranes of different tensions.
    Biophys J. 2000 May;78(5):2241-56 PMID: 10777723
  55. Inhibition of SNARE complex assembly differentially affects kinetic components of exocytosis.
    Cell. 1999 Dec 23;99(7):713-22 PMID: 10619425
  56. Structure and function of fusion pores in exocytosis and ectoplasmic membrane fusion.
    Curr Opin Cell Biol. 1995 Aug;7(4):509-17 PMID: 7495570
  57. Fusion pores and fusion machines in Ca2+-triggered exocytosis.
    Annu Rev Biophys Biomol Struct. 2006;35:135-60 PMID: 16689631
  58. The synaptic SNARE complex is a parallel four-stranded helical bundle.
    Nat Struct Biol. 1998 Sep;5(9):765-9 PMID: 9731768
  59. Sequential N- to C-terminal SNARE complex assembly drives priming and fusion of secretory vesicles.
    EMBO J. 2006 Mar 8;25(5):955-66 PMID: 16498411
Article Info
Journal
The Journal of membrane biology
Abbr.
J Membr Biol
ISSN
1432-1424
Published
2010-06-00
Epub
2010-00-30
Pages
89-100
Language
English
Region
United States
NLM ID
0211301
PMCID
PMC2944410
Subset
IM
Grants
NINDS NIH HHS · NS44057 · United States
NINDS NIH HHS · R01 NS044057-08 · United States
NINDS NIH HHS · R01 NS044057-09 · United States
NINDS NIH HHS · R01 NS044057 · United States
NINDS NIH HHS · R01 NS044057-07 · United States
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com