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#SNARE complex

8 public questions tagged with this topic.

Protein Sorting and Trafficking

What is the role of NSF in membrane fusion?

Secretory pathway maintains SNARE availability through constant recycling machinery whose energy source ATP hydrolysis by NSF. After lipid merger SNARE proteins locked in four-helix bundle cis-complex embedded single target membrane deep energy well impossible separate spontaneously. To regenerate fusion-competent monomers ATP-driven chaperone required. Hexameric N-ethylmaleimide sensitive factor NSF 76 kDa per protomer double ring structure associates via adaptor alpha-SNAP decorating outside SNARE rod tetramer coating. Each SNAP C-terminus contacts one N-domain NSF hexamer forming 20S partic

Ref: Alberts et al., MBC: NSF hydrolyzes ATP to disassemble cis-SNARE complexes.

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Protein Sorting and Trafficking

Which protein facilitates vesicle uncoating after transport?

Temporal control coat association ensures vesicle budding but permits subsequent fusion because SNAREs hidden under coat cannot engage target. After detachment coat must be shed within seconds exposing v-SNAREs for tethering. Distinct uncoating mechanisms evolved: COPII shedding triggered by Sar1 GTP hydrolysis stimulated by Sec23 GAP plus Sec13-31 destabilization; COPI shedding by ARF GAP1/2 ASAP stimulating ARF1 hydrolysis plus curvature mismatch. Clathrin uncoating for AP2 and AP1/GGA vesicles requires chaperone system unique: DnaJ co-chaperone auxilin 1/2 specifically recognizes assembled

Ref: Sousa & Lafer, Traffic 2015: Hsc70 and auxilin mediate clathrin uncoating.

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Protein Sorting and Trafficking

What is the function of α-SNAP?

Alpha-SNAP soluble attachment protein family 35 kDa containing N-terminal helical bundle and C-terminal tetratricopeptide repeats serving adaptor for NSF ATPase. After fusion four-helix cis-SNARE complex remains tightly intertwined embedded in acceptor membrane extremely stable. Alpha-SNAP tetramer binds along outer surface grooves via charged interactions each molecule providing C-terminal leucine repeat interface for one N-domain of hexameric NSF oligomer. Once six N-domains engage four SNAPs 20S supercomplex forms stabilized by ATP bound non-hydrolyzable state where SNAP orientation present

Ref: Alberts et al., MBC Chapter 13: alpha-SNAP and NSF recycle SNAREs after fusion.

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Protein Sorting and Trafficking

Which factor is required for dissociation of the SNARE complex?

After fusion membrane-embedded SNARE complex ends up as cis-complex where all helices reside in same membrane representing dead-end product incapable of further fusion blocking availability. To maintain flux complex must be disassembled into monomers. Alpha-SNAP adaptor family including alpha, beta, gamma isoforms binds along four-helix bundle recognizing charge pattern; up to four molecules coat complex serving landing pad for hexameric NSF ATPase. NSF contains N-terminal substrate binding domains, D1 ATPase providing mechanical power and D2 stabilizing hexamer. ATP hydrolysis in D1 hydrolyzi

Ref: Alberts et al., MBC: NSF ATPase disassembles SNARE complexes post-fusion for recycling.

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Protein Sorting and Trafficking

What is the function of SNAP-25 in vesicle fusion?

Assembly of heteromeric SNARE core provides mechanical work for fusion in neurons, endocrine cells and constitutive secretion. Proteins classified into Q-SNAREs supplying glutamine at central zero ionic layer and R-SNAREs supplying arginine. Target plasma membrane harbors two Q proteins: syntaxin1 integral with single Q helix preceded by Habc regulatory domain clamped by Munc18 and SNAP-25 peripheral anchored via palmitoylated linker contributing two Q helices lacking transmembrane domain together contributing three Q motifs collectively t-SNARE. Vesicle membrane supplies R protein synaptobrev

Ref: Jahn & Scheller, Nat Rev Mol Cell Biol: SNAP-25 as Qbc t-SNARE in fusion.

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Protein Sorting and Trafficking

What triggers the disassembly of SNARE complexes after membrane fusion?

Cis-SNARE complexes formed post-fusion are extremely stable four-helix bundles with melting temperature above 90 Celsius requiring energy for recycling. Disassembly machinery uses ATP. Hexameric AAA+ ATPase NSF N-ethylmaleimide sensitive factor assembles as ring with two stacked ATPase tiers D1 catalytic and D2 structural. Adaptor alpha-SNAP soluble attachment protein binds grooves along rod-like bundle via tetratricopeptide repeats and recruits NSF via N domains interaction with SNAP C-terminus. ATP hydrolysis in D1 causes power stroke threading SNARE polypeptide through central pore with tyr

Ref: Lodish et al., MCB Chapter 14: NSF and alpha-SNAP disassemble cis-SNARE complexes via ATP hydrolysis.

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Protein Sorting and Trafficking

What is the function of the SNARE complex?

Vesicle fusion fidelity beyond tethering relies on SNARE proteins providing thermodynamic driver for bilayer merger overcoming hydration repulsion. Vesicle membranes contain R-SNAREs like synaptobrevin VAMP2 with single motif and C-terminal anchor, while target membranes harbor Q-SNAREs syntaxin family with Habc regulatory domain and SNAP-25 family contributing two motifs anchored by palmitoylation. When opposed membranes brought within few nanometers by Rab tethers and multisubunit complexes, oppositely oriented SNARE motifs assemble as parallel four-helix coiled coil from N-terminus to C-ter

Ref: Jahn & Scheller, Nat Rev Mol Cell Biol 2006: SNARE four-helix bundle drives membrane fusion.

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Protein Sorting and Trafficking

What is the function of the SNARE complex in vesicular transport?

Final step of vesicular traffic requires merging of two lipid bilayers normally separated by hydration repulsion and electrostatic forces. SNARE proteins provide mechanical work through formation of extremely stable coiled-coil bundle. Vesicle-anchored R-SNAREs like VAMP2/synaptobrevin carry single SNARE motif with arginine at ionic layer, while target membrane Q-SNAREs syntaxin-1 and SNAP-25 contribute three motifs with glutamine at ionic layer; together they zipper progressively from membrane-distal N termini toward membrane-proximal C termini into parallel four-helix bundle releasing energy

Ref: Alberts et al., Molecular Biology of the Cell, 6th ed., Chapter 13: SNARE Complex Mediating Membrane Fusion.

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