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| [[Image:Exocytosis-machinery.jpg|thumb|360px|right|Molecular machinery driving [[vesicle fusion]] in neuromediator release. The core SNARE complex is formed by four α-helices contributed by synaptobrevin, syntaxin and SNAP-25, synaptotagmin serves as a calcium sensor and regulates intimately the SNARE zipping]]
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| '''SNARE''' (an [[acronym]] derived from "'''SNA'''P (Soluble [[N-ethylmaleimide Sensitive Factor or fusion protein|NSF]] Attachment Protein) '''RE'''ceptor") '''proteins''' are a large protein superfamily consisting of more than 60 members in yeast and mammalian cells.<ref name="gerald2002">
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| {{cite journal
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| | author = Gerald K
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| | title = Cell and Molecular Biology (4th edition)
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| | journal = John Wiley & Sons, Inc.
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| | volume =
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| | pages =
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| | year = 2002
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| }}
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| </ref>
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| The primary role of SNARE proteins is to mediate [[vesicle fusion]], that is, the [[exocytosis]] of cellular [[vesicle (biology)|transport vesicles]] with the [[cell membrane]] at the [[porosome]] or with a target compartment (such as a [[lysosome]]).
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| SNAREs can be divided into two categories: ''vesicle'' or ''v-SNAREs'', which are incorporated into the membranes of transport vesicles during budding, and ''target'' or ''t-SNAREs'', which are located in the membranes of target compartments.
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| Recent classification however takes account of the structural features of the SNARE proteins and divides them into R-SNAREs and Q-SNAREs.
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| The best-studied SNAREs are those that mediate docking of [[Synaptic vesicle|Synaptic Vesicles]] with the presynaptic membrane. These SNAREs are the targets of the bacterial neurotoxins responsible for [[botulism]] and [[tetanus]].
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| SNAREs are small, abundant and mostly plasma membrane-bound proteins. Although they vary considerably in structure and size, all share a segment in their [[cytosol]]ic domain called a ''SNARE motif'' that consists of 60-70 [[amino acid]]s that are capable of reversible assembly into tight, four-helix bundles called ''"trans"-SNARE complexes''.
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| The readily-formed [[metastability in molecules|metastable]] "trans" complexes are composed of three SNAREs: [[syntaxin 1]] and [[SNAP-25]] resident in cell membrane and [[synaptobrevin]] (also referred to as [[vesicle-associated membrane protein]] or VAMP) anchored in the vesicular membrane.
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| In [[neuron]]al [[exocytosis]], [[syntaxin]] and [[synaptobrevin]] are anchored in respective membranes by their C-terminal domains, whereas [[SNAP-25]] is tethered to the plasma membrane via several cysteine-linked [[palmitoyl chains]]. The core SNARE complex is a four-<math>\alpha</math>-helix bundle, where one <math>\alpha</math>-helix is contributed by syntaxin-1, one <math>\alpha</math>-helix by synaptobrevin and two <math>\alpha</math>-helices are contributed by SNAP-25.
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| The plasma membrane-resident SNAREs have been shown to be present in distinct microdomains or clusters, the integrity of which is essential for the exocytotic competence of the cell.
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| ==SNARE complexes==
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| [[Image:Zerolayer.png|frame|right|Layering of the core SNARE complex. In the center is the zero hydrophilic ionic layer, flanked by hydrophobic leucine-zipper layers.]]
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| During membrane fusion, the SNARE proteins involved combine to form a ''SNARE complex''. Depending on the stage of fusion of the host vesicles, these complexes may be referred to differently.
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| ''"Trans"-SNARE complexes'' are [[protein]] complexes composed of three [[SNARE proteins]] anchored in opposing (or ''[[trans]]'') membranes ''prior'' to membrane fusion. During fusion, the membranes merge and SNARE proteins involved in complex formation after fusion are then referred to as a ''"cis"-SNARE complex'', because they now reside in a single (or ''[[cis]]'') resultant membrane.
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| ==R-SNAREs==
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| ''R-SNAREs'' are proteins that contribute an [[arginine]] (R) residue in the formation of the ''zero ionic layer'' in the assembled core SNARE complex. One particular R-SNARE is [[synaptobrevin]], which is located in the synaptic vesicles.
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| ==Q-SNAREs==
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| ''Q-SNAREs'' are proteins that contribute a [[glutamine]] (Q) residue in the formation of the ''zero ionic layer'' in the assembled core SNARE complex. Q-SNAREs include [[syntaxin]] and [[SNAP-25]].
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| ==Other components==
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| The core SNARE complex is a 4-<math>\alpha</math>-helix bundle.<ref name="sutton1998">
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| {{cite journal
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| | author = Sutton RB, Fasshauer D, Jahn R, Brünger AT
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| | title = Crystal structure of a SNARE complex involved in synaptic exocytosis at 2.4 Å resolution
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| | journal = Nature
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| | volume = 395
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| | pages = 347–353
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| | year = 1998
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| | doi = 10.1038/26412
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| | pmid = 9759724
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| | issue = 6700
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| | url=http://atb.slac.stanford.edu/public/papers.php?sendfile=66
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| }}
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| </ref> Synaptobrevin and syntaxin contribute one <math>\alpha</math>-helix each, while SNAP-25 participates with two <math>\alpha</math>-helices (abbreviated as Sn1 and Sn2). The interacting amino acid residues that zip the SNARE complex can be grouped into layers. Each layer has 4 amino acid residues - one residue per each of the 4 <math>\alpha</math>-helices. In the center of the complex is the ''zero ionic layer'' composed of one arginine (R) and three glutamine (Q) residues, and it is flanked by [[leucine zippering]]. Layers '-1', '+1' and '+2' at the centre of the complex most closely follow ideal leucine-zipper geometry and aminoacid composition.<ref name="fass1998">
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| {{cite journal
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| | author = Fasshauer D, Sutton RB, Brunger AT, Jahn R
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| | title = Conserved structural features of the synaptic fusion complex: SNARE proteins reclassified as Q- and R-SNAREs
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| | journal = Proceedings of the National Academy of Sciences
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| | volume = 95
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| | pages = 15781–15786
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| | year = 1998
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| | doi = 10.1073/pnas.95.26.15781
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| | pmid = 9861047
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| | issue = 26
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| | pmc = 28121
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| | url=http://www.pnas.org/cgi/content/full/95/26/15781
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| }}
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| </ref>
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| The ''zero ionic layer'' is composed of R56 from VAMP-2, Q226 from syntaxin-1A, Q53 from Sn1 and Q174 from Sn2, and is completely buried within the leucine-zipper layers. The positively charged [[guanidino]] group of the [[arginine]] (R) residue interact with the [[carboxyl]] groups of each of the three [[glutamine]] (Q) residues.
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| The flanking leucine-zipper layers act as a water-tight seal to shield the [[Ionic bond|ionic interactions]] from the surrounding [[solvent]]. Exposure of the ''zero ionic layer'' to the water solvent by breaking the flanking leucine zipper leads to instability of the SNARE complex and is the putative mechanism by which <math>\alpha</math>-SNAP and [[N-ethylmaleimide sensitive fusion protein|NSF]] recycle the SNARE complexes after the completion of [[synaptic vesicle]] [[exocytosis]].
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| ==Proposed mechanism of membrane fusion==
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| Assembly of the SNAREs into the "trans" complexes likely bridges the opposing lipid bilayers of membranes belonging to cell and secretory granule, bringing them in proximity and inducing their fusion. The influx of calcium into the cell triggers the completion of the assembly reaction, which is mediated by an interaction between the putative calcium sensor, [[synaptotagmin]], with membrane lipids and/or the partially assembled
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| SNARE complex.
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| According to the [["zipper" hypothesis]], the complex assembly starts at the N-terminal parts of SNARE motifs and proceeds towards the C-termini that anchor interacting proteins in membranes. Formation of the "trans"-SNARE complex proceeds through an intermediate complex composed of SNAP-25 and syntaxin-1, which later accommodates synaptobrevin-2 (the quoted syntaxin and synaptobrevin isotypes participate in neuronal neuromediator release).
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| Based on the stability of the resultant ''cis-SNARE complex'', it has been postulated that energy released during the assembly process serves as a means for overcoming the repulsive forces between the membranes. There are several models that propose explanation of a subsequent step – the formation of stalk and [[porosome|fusion pore]], but the exact nature of these processes remains debated. A recent ''in vitro'' single-molecule content-mixing study showed that yeast SNARE complex is enough to expand fusion pores.<ref>name="diao2010"</ref>
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| According to the "clamp" hypothesis, a reversible clamping protein (known as complexin), inhibits synaptic vesicle fusion. When calcium binds to the calcium sensor [[synaptotagmin]], the clamp would then be released. SNARE proteins, and key regulators like [[synaptotagmin]] and complexin, act as markers on the cell membrane. Cells expressing such “flipped” synaptic SNARE switches fuse constitutionally. However, when the expression of complexin blocked fusion alone. When calcium was added back, the cell began to exhibit fusion. This suggests that [[synaptotagmin]] and complexin may be co-regulators in synaptic vesicle fusion.<ref>{{pmid|16794037}}</ref>
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| However, recent evidence including detailed structural and functional studies have proposed that SNAREs mostly function in accord with the "zipper" model. Nevertheless, it remains unclear whether SNARE assembly between membranes directly leads to the merger of lipid bilayers.<ref>{{pmid|12914950}}</ref>
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| ==Toxins==
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| Many [[neurotoxin]]s directly affect SNARE complexes. Such toxins as the [[Botulinum toxin|Botulinum]] and [[Tetanus]] toxins work by targeting the SNARE components. These toxins prevent proper vesicle recycling and result in poor muscle control, spasms, paralysis and even death.
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| Specifically, the [[Botulinum toxin]] attacks the SNAP-25 protein of the SNARE complex. The [[Botulinum toxin]] degrades and cleaves the SNAP-25 protein, a protein that is required for vesicle fusion that releases neurotransmitters. Botulinum essentially cleaves these SNARE proteins, and in doing so, prevents synaptic vesicles from fusing with the cellular synaptic membrane and releasing their neurotransmitters.
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| The Tetanus toxin follows a similar pathway, but instead attacks the protein synaptobrevin on the synaptic vesicle.
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| These toxins result in acquiring [[Tetanus]], a medical condition characterized by a prolonged contraction of skeletal muscle fibers and [[Botulism]], a type of food poisoning that in severe forms, can lead to muscle paralysis including breathing muscles, which causes respiratory failure.
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| ==References==
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| {{reflist|2}}
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| ==External links==
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| * {{MeshName|SNARE+Proteins}}
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| * {{MeshName|SNARE+Complex}}
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| {{Vesicular transport proteins}}
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| [[Category:Transmembrane proteins]]
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| [[Category:Protein families]]
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| [[Category:Neurophysiology]]
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I would like to introduce myself to you, I am Andrew and my wife doesn't like it at all. Since he was 18 he's been working as an info officer but he ideas on altering it. To climb is some thing she would never give up. North Carolina is where we've been living for years and will by no means transfer.
Here is my webpage - email psychic readings