関: SNARE、soluble NSF attachment protein receptor

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a trap for birds or small mammals; often has a slip noose (同)gin, noose
a surgical instrument consisting of wire hoop that can be drawn tight around the base of polyps or small tumors to sever them; used especially in body cavities
strings stretched across the lower head of a snare drum; they make a rattling sound when the drum is hit
any of a large group of nitrogenous organic compounds that are essential constituents of living cells; consist of polymers of amino acids; essential in the diet of animals for growth and for repair of tissues; can be obtained from meat and eggs and milk and legumes; "a diet high in protein"

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(小動物を捕らえる)『わな』《+『for』+『名』》 / (人を陥れる)『わな』,落とし穴《+『for』+『名』》 / 〈小動物〉‘を'わなにかける〈人〉‘を'わなにかける,陥れる
(小太鼓の)さわり弦,響線
蛋白(たんばく)質

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/12/13 16:22:34」(JST)

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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

SNARE (an acronym derived from "SNAP (Soluble NSF Attachment Protein) REceptor") proteins are a large protein superfamily consisting of more than 60 members in yeast and mammalian cells.^[1]

The primary role of SNARE proteins is to mediate vesicle fusion, that is, the exocytosis of cellular transport vesicles with the cell membrane at the porosome or with a target compartment (such as a lysosome).

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.

Recent classification however takes account of the structural features of the SNARE proteins and divides them into R-SNAREs and Q-SNAREs.

The best-studied SNAREs are those that mediate docking of Synaptic Vesicles with the presynaptic membrane. These SNAREs are the targets of the bacterial neurotoxins responsible for botulism and tetanus.

SNAREs are small, abundant and mostly plasma membrane-bound proteins. Although they vary considerably in structure and size, all share a segment in their cytosolic domain called a SNARE motif that consists of 60-70 amino acids that are capable of reversible assembly into tight, four-helix bundles called "trans"-SNARE complexes.

The readily-formed 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.

In neuronal 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--helix bundle, where one -helix is contributed by syntaxin-1, one -helix by synaptobrevin and two -helices are contributed by SNAP-25.

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.

SNARE complexes[edit]

Layering of the core SNARE complex. In the center is the zero hydrophilic ionic layer, flanked by hydrophobic leucine-zipper layers.

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.

"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.

R-SNAREs[edit]

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.

Q-SNAREs[edit]

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.

Other components[edit]

The core SNARE complex is a 4--helix bundle.^[2] Synaptobrevin and syntaxin contribute one -helix each, while SNAP-25 participates with two -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 -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.^[3]

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.

The flanking leucine-zipper layers act as a water-tight seal to shield the 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 -SNAP and NSF recycle the SNARE complexes after the completion of synaptic vesicle exocytosis.

Proposed mechanism of membrane fusion[edit]

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 SNARE complex.

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).

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 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.^[4]

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.^[5]

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.^[6]

Toxins[edit]

Many neurotoxins directly affect SNARE complexes. Such toxins as the 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.

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. The Tetanus toxin follows a similar pathway, but instead attacks the protein synaptobrevin on the synaptic vesicle.

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.

References[edit]

^ Gerald K (2002). "Cell and Molecular Biology (4th edition)". John Wiley & Sons, Inc.
^ Sutton RB, Fasshauer D, Jahn R, Brünger AT (1998). "Crystal structure of a SNARE complex involved in synaptic exocytosis at 2.4 Å resolution". Nature 395 (6700): 347–353. doi:10.1038/26412. PMID 9759724.
^ Fasshauer D, Sutton RB, Brunger AT, Jahn R (1998). "Conserved structural features of the synaptic fusion complex: SNARE proteins reclassified as Q- and R-SNAREs". Proceedings of the National Academy of Sciences 95 (26): 15781–15786. doi:10.1073/pnas.95.26.15781. PMC 28121. PMID 9861047.
^ name="diao2010"
^ Giraudo, C. G.; Eng, W. S.; Melia, T. J.; Rothman, J. E. (2006). "A Clamping Mechanism Involved in SNARE-Dependent Exocytosis". Science 313 (5787): 676–680. doi:10.1126/science.1129450. PMID 16794037. edit
^ Fasshauer, D. (2003). "Structural insights into the SNARE mechanism". Biochimica et biophysica acta 1641 (2–3): 87–97. doi:10.1016/S0167-4889(03)00090-9. PMID 12914950. edit

External links[edit]

SNARE Proteins at the US National Library of Medicine Medical Subject Headings (MeSH)
SNARE Complex at the US National Library of Medicine Medical Subject Headings (MeSH)

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A closer look to botulinum neurotoxin type A-induced analgesia.

Guo BL, Zheng CX, Sui BD, Li YQ, Wang YY, Yang YL.SourceDepartment of Anatomy and K.K. Leung Brain Research Centre, Fourth Military Medical University, Xi'an 710032, People's Republic of China; Medical Student, School of Stomatology, The Fourth Military Medical University, Xi'an, China.
Toxicon : official journal of the International Society on Toxinology.Toxicon.2013 Sep;71:134-9. doi: 10.1016/j.toxicon.2013.05.011. Epub 2013 Jun 5.
Chronic pain indicates a type of pain that lasts over time and is accompanied by diagnostic and therapeutic difficulties. It follows that treatment failures are common and patients roam from doctor to doctor in search of an effective care program. So there is an urgent need for long-acting and effec
PMID 23747735

VAMP4 is required to maintain the ribbon structure of the Golgi apparatus.

Shitara A, Shibui T, Okayama M, Arakawa T, Mizoguchi I, Shakakura Y, Takuma T.SourceDivision of Biochemistry, Department of Oral Biology, School of Dentistry, Health Sciences University of Hokkaido, Tobetsu Hokkaido, Ishikari, 061-0293, Japan, shitara@hoku-iryo-u.ac.jp.
Molecular and cellular biochemistry.Mol Cell Biochem.2013 Aug;380(1-2):11-21. doi: 10.1007/s11010-013-1652-4. Epub 2013 May 16.
The Golgi apparatus forms a twisted ribbon-like network in the juxtanuclear region of vertebrate cells. Vesicle-associated membrane protein 4 (VAMP4), a v-SNARE protein expressed exclusively in the vertebrate trans-Golgi network (TGN), plays a role in retrograde trafficking from the early endosome t
PMID 23677696

A conserved, 1:1 interaction between α-SNAP and t-SNAREs initiates disassembly of all SNARE complexes by the N-ethylmaleimide sensitive factor (NSF).

Vivona S, Cipriano DJ, O Leary S, Li YH, Fenn TD, Brunger AT.SourceStanford University, United States.
The Journal of biological chemistry.J Biol Chem.2013 Jul 8. [Epub ahead of print]
Vesicle trafficking in eukaryotic cells is facilitated by SNARE-mediated membrane fusion. The ATPase NSF and the adapter protein α-SNAP disassemble all SNARE complexes formed throughout different pathways, but the effect of SNARE sequence and domain variation on the poorly understood disassembly me
PMID 23836889

Japanese Journal

Schizosaccharomyces pombe Pep12p is required for vacuolar protein transport and vacuolar homotypic fusion(GENETICS, MOLECULAR BIOLOGY, AND GENE ENGINEERING)

Hosomi Akira,Nakase Mai,Takegawa Kaoru
Journal of bioscience and bioengineering 112(4), 309-314, 2011-10
… In eukaryotic cells, SNARE proteins are essential for intracellular vesicle trafficking. … Several SNARE proteins are required for vacuolar protein transport and vacuolar biogenesis in Saccharomyces cerevisiae. … Previously we demonstrated that one of the fission yeast SNARE proteins, Pep12p, is not required for vacuolar fusion process in Schizosaccharomyces pombe. …
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Functional molecular morphology of anterior pituitary cells, from hormone production to intracellular transport and secretion

MATSUNO Akira,MIZUTANI Akiko,OKINAGA Hiroko,TAKANO Koji,YAMADA So,YAMADA Shoko M.,NAKAGUCHI Hiroshi,HOYA Katsumi,MURAKAMI Mineko,TAKEUCHI Masato,SUGAYA Mutsumi,ITOH Johbu,TAKEKOSHI Susumu,OSAMURA R. Yoshiyuki
Medical molecular morphology : official journal of the Japanese Society for Clinical Molecular Morphology 44(2), 63-70, 2011-06-01
NAID 10029036664

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★リンクテーブル★

リンク元	「SNAREタンパク質」「可溶性N-エチルマレイミド感受性因子付着タンパク質受容体」「soluble NSF attachment protein receptor」「SNARE蛋白質」
拡張検索	「R-SNARE protein」「Qa-SNARE protein」