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The SNARE fusion complex, fusing neurotransmitter vesicles with the presynaptic membrane. Ca2+ acts on the synaptic vesicle synaptotagmin1 (synaptotagmin I; SytI, Syt1, SSVP65, SYT) to trigger rapid exocytosis (Chapman, 2008).  Syt1 is a major Ca2+ sensor for fast neurotransmitter release. It contains tandem Ca2+-binding C2 domains (C2AB), a single transmembrane α-helix and a highly charged 60-residue- long linker in between. The linker region of Syt1 is essential for its two signature functions: Ca2+-independent vesicle docking and Ca2+-dependent fusion pore opening. The linker contains the basic-amino acid-rich N-terminal region and the acidic amino acid-rich C-terminal region (Lai et al. 2013).  The intrinsically disordered region between Syt I's transmembrane helix and the first C2 domain interats with vesicular lipids and modulates Ca2+ binding to C2 (Fealey et al. 2016). t-SNARE and v-SNARE interact in their C-terminal TMSs to promote pore opening (Wu et al. 2016).  Both sides of a trans-SNARE complex can drive pore opening suggesting an indentation model in which multiple SNARE C-termini cooperate in opening the fusion pore by locally deforming the inner leaflets (D'Agostino et al. 2016).

The ten component SNARE fusion complex of Homo sapiens, fusing neurotransmitter vesicles with the presynaptic membrane.

Yeast vacuolar snare complex including the vesicle-associated membrane protein 2 (Snc2p; 115aas; 1-C-terminal TMS) (Chernomordik et al., 2005), the vacuole morphogenesis protein, Vam3 (PTH1) of 283 aas, the vacuolar v-snare, Nyv1 of 253 aas, and the t-snare, Vti1 of 217 aas. Considering these last three proteins, SNARE TMSs serve as non-specific membrane anchors in vacuole fusion, but fusion requires the SNARE complexes in the plasma and vacuolar membranes. Lipid-anchored Vti1 was fully active, lipid-anchored Nyv1 (R-SNARE) permitted the fusion reaction to proceed up to hemifusion, but lipid-anchored Vam3 interfered with fusion before hemifusion. Vam7 (a soluble SNARE; 316 aas) and Sec18 (758 aas) remodel SNARE compexes to allow lipd-anchored R-SNARE (NYV1, 253 aas), acting with Q-SNARE (VTS1; 523 aas), to support vacuole fusion (Jun et al. 2007).Thus, these proteins have non-specific membrane anchors, but each of these proteins makes different contributions to the hemifusion intermediate and opening of the fusion pore (Semenov et al. 2014).

The vacuolar snare complex of Saccharomyces cerevisiae (P33328)

The worm SNARE complex and it's regulators for vesicle neurotransmetter and neuropeptide release (Gracheva et al. 2007).  The SNARE complex consists of Syntaxin, SNAP and Synaptobrevin and mediates the synaptic vesicle cycle (Rathore et al. 2010).  Synaptotagmin I is a Ca2+ sensor triggering vesicle fusion (Yu et al. 2013).  Regulators include Snapin dimers (Yu et al. 2013), Complexin, a presynaptic protein that interacts with the SNARE complex; the C-terminal domain binds lipids to inhibit exocytosis (Hobson et al. 2011; Wragg et al. 2013), Unc-18, which binds syntaxin and regluates synaptic vesicle (neurotransmitter) docking (Graham et al. 2011), Unc13 which also regluates docking of the synaptic vescicles to the plasma membrane by interacting with syntaxin, CAPS or Unc31, a Ca2+-activated protein for secretion that is required for dense core vesicle docking for neuropeptide release (Lin et al. 2010), and Tomosyn or Tom-1, a negative regluator of both neurotransmitter and neuropeptide release (Gracheva et al. 2007).

Synaptic vesicle fusion apparatus of Caenorhabditis elegans

The mouse synaptobrevin 2 (syb2)/VAMP2/Syntaxin (Syx)/SNAP-25 complex involved in vesicle fusion pore formation (Chang et al. 2015). The synaptobrevin juxtamembrane regions plus the TMS may catalyze pore formation by forming a membrane-spanning complex that increases curvature stress at the circumference of the hemifused diaphragm of the prepore intermediate state (Tarafdar et al. 2015). The TMS of VAMP2 plays a critical role membrane fusion, and the structural mobility provided by the central small amino acids is crucial for exocytosis by influencing the molecular re-arrangements of the lipid membrane that are necessary for fusion pore opening and expansion (Hastoy et al. 2017).

Fusion pore forming subunits of Mus musculus
Synaptobrevin-2 (Syb2; Vamp2) of 116 aas and one C-terminal TMS
Syntaxin (SyxB) of 236 aas and one C-terminal TMS
Synaptosomal-associated portein, Snap-25 of 206 aa and 0 TM  

Dysferlin/Caveolin 3/MG53 (TRIM72) complex.  Mediates vesicle fusion and membrane repair in muscle cells (Fuson et al. 2014).  Dysferlin (DysF; Fer1L1) belongs to the Ferlin family.  A deficiency of dysferlin, which binds lipids in a Ca2+-dependent process, causes vesicle accumulation near membrane lesions (Roostalu and Strähle 2012). 

Dysferlin (DysF; Fer1L1)/Caveolin 3/MG53 (TRIM72) complex of Homo sapiens.
Dysferlin (2080 aas; O75923)
Caveolin 3 (151 aas; P56539)
MG53 (477 aas; Q6ZMU5)