Database accession: MF4210003
Name: Endosomal SNARE core complex (Syntaxin-1A / SNAP25)
PDB ID: 1jth
Experimental method: X-ray (2.00 Å)
Assembly: Heterotetramer
Source organism: Rattus norvegicus
Primary publication of the structure:
Misura KM, Gonzalez LC, May AP, Scheller RH, Weis WI
Crystal structure and biophysical properties of a complex between the N-terminal SNARE region of SNAP25 and syntaxin 1a.
(2001) J. Biol. Chem. 276: 41301-9
PMID: 11533035
Abstract:
SNARE proteins are required for intracellular membrane fusion. In the neuron, the plasma membrane SNAREs syntaxin 1a and SNAP25 bind to VAMP2 found on neurotransmitter-containing vesicles. These three proteins contain "SNARE regions" that mediate their association into stable tetrameric coiled-coil structures. Syntaxin 1a contributes one such region, designated H3, and SNAP25 contributes two SNARE regions to the fusogenic complex with VAMP2. Syntaxin 1a H3 (syn1aH3) and SNAP25 can form a stable assembly, which can then be bound by VAMP2 to form the full SNARE complex. Here we show that syn1aH3 can also form a stable but kinetically trapped complex with the N-terminal SNARE region of SNAP25 (S25N). The crystal structure of this complex reveals an extended parallel four-helix bundle similar to that of the core SNARE and the syn1aH3-SNAP25 complexes. The inherent ability of syn1aH3 and S25N to associate stably in vitro implies that the intracellular fusion machinery must prevent formation of, or remove, any non-productive complexes. Comparison with the syn1aH3-SNAP25 complex suggests that the linkage of the N- and C-terminal SNAP25 SNARE regions is kinetically advantageous in preventing formation of the non-productive syn1aH3-S25N complex. We also demonstrate that the syn1aH3-S25N complex can be disassembled by alpha-SNAP and N-ethylmaleimide-sensitive factor.
Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown. Molecular function:
calcium-dependent protein binding calcium-dependent protein binding
myosin binding myosin binding
SNAP receptor activity SNAP receptor activity
SNARE binding SNARE binding
transmembrane transporter binding transmembrane transporter binding
Biological process:
exocytosis exocytosis
SNARE complex assembly SNARE complex assembly
synaptic vesicle exocytosis synaptic vesicle exocytosis
synaptic vesicle fusion to presynaptic active zone membrane synaptic vesicle fusion to presynaptic active zone membrane
Cellular component:
axon axon
glutamatergic synapse glutamatergic synapse
membrane membrane
neuron projection neuron projection
plasma membrane plasma membrane
presynapse presynapse
presynaptic active zone membrane presynaptic active zone membrane
presynaptic membrane presynaptic membrane
SNARE complex SNARE complex
synapse synapse
synaptic vesicle synaptic vesicle
synaptobrevin 2-SNAP-25-syntaxin-1a complex synaptobrevin 2-SNAP-25-syntaxin-1a complex
synaptobrevin 2-SNAP-25-syntaxin-1a-complexin I complex synaptobrevin 2-SNAP-25-syntaxin-1a-complexin I complex
synaptobrevin 2-SNAP-25-syntaxin-1a-complexin II complex synaptobrevin 2-SNAP-25-syntaxin-1a-complexin II complex
Structural annotations of the participating protein chains.Entry contents: 4 distinct polypeptide molecules
Chains: A, B, C, D
Notes: All chains according to the most probable oligomerization state stored in PDBe were considered.
Number of unique protein segments: 2
Name: Synaptosomal-associated protein 25
Source organism: Rattus norvegicus
Length: 206 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMAEDADMRNELEEMQRRADQLADESLESTRRMLQLVEESKDAGIRTLVMLDEQGEQLERIEEGMDQINKDMKEAEKNLTDLGKFCGLCVCPCNKLKSSDAYKKAWGNNQDGVVASQPARVVDEREQMAISGGFIRRVTNDARENEMDENLEQVSGIIGNLRHMALDMGNEIDTQNRQIDRIMEKADSNKTRIDEANQRATKMLGSG
UniProtKB AC: P60881 (positions: 11-72)
Coverage: 30%
Name: Syntaxin-1A
Source organism: Rattus norvegicus
Length: 288 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMKDRTQELRTAKDSDDDDDVTVTVDRDRFMDEFFEQVEEIRGFIDKIAENVEEVKRKHSAILASPNPDEKTKEELEELMSDIKKTANKVRSKLKSIEQSIEQEEGLNRSSADLRIRKTQHSTLSRKFVEVMSEYNATQSDYRERCKGRIQRQLEITGRTTTSEELEDMLESGNPAIFASGIIMDSSISKQALSEIETRHSEIIKLENSIRELHDMFMDMAMLVESQGEMIDRIEYNVEHAVDYVERAVSDTKKAVKYQSKARRKKIMIIICCVILGIIIASTIGGIFG
UniProtKB AC: P32851 (positions: 191-257)
Coverage: 23%
Name: Synaptosomal-associated protein 25
Source organism: Rattus norvegicus
Length: 206 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMAEDADMRNELEEMQRRADQLADESLESTRRMLQLVEESKDAGIRTLVMLDEQGEQLERIEEGMDQINKDMKEAEKNLTDLGKFCGLCVCPCNKLKSSDAYKKAWGNNQDGVVASQPARVVDEREQMAISGGFIRRVTNDARENEMDENLEQVSGIIGNLRHMALDMGNEIDTQNRQIDRIMEKADSNKTRIDEANQRATKMLGSG
UniProtKB AC: P60881 (positions: 10-78)
Coverage: 33%
Name: Syntaxin-1A
Source organism: Rattus norvegicus
Length: 288 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMKDRTQELRTAKDSDDDDDVTVTVDRDRFMDEFFEQVEEIRGFIDKIAENVEEVKRKHSAILASPNPDEKTKEELEELMSDIKKTANKVRSKLKSIEQSIEQEEGLNRSSADLRIRKTQHSTLSRKFVEVMSEYNATQSDYRERCKGRIQRQLEITGRTTTSEELEDMLESGNPAIFASGIIMDSSISKQALSEIETRHSEIIKLENSIRELHDMFMDMAMLVESQGEMIDRIEYNVEHAVDYVERAVSDTKKAVKYQSKARRKKIMIIICCVILGIIIASTIGGIFG
UniProtKB AC: P32851 (positions: 195-245)
Coverage: 17%
Evidence demonstrating that the participating proteins are unstructured prior to the interaction and their folding is coupled to binding. Representative domain in related structures: -
Evidence level: Direct evidence
Evidence coverage: The full structure participates in mutual synergistic folding.
Complex Evidence:
The structure shows the core domain of a SNARE complex (PMID:11533035). SNARE complexes are formed by the parallel arrangement of four protein chains bound by coiled-coil interactions forming a four helix bundle (PMID:9390521). Coiled coils are highly versatile folding units (PMID:11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID:9811815) and trimers (PMID:10933510) up to heptamers (PMID:17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID:8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID:17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure.
Chain A:
The region(s) described in DP00068 covers 100% of the sequence present in the structure
Chain B:
N/A
Chain C:
The region(s) described in DP00068 covers 100% of the sequence present in the structure
Chain D:
N/A
Surface and contacts features:
Structures from the PDB that contain the same number of proteins, and the proteins from the two structures show a sufficient degree of pairwise similarity, i.e. they belong to the same UniRef90 cluster (the full proteins exhibit at least 90% sequence identity) and convey roughly the same region to their respective interactions (the two regions from the two proteins share a minimum of 70% overlap). No related structure was found in the MFIB database.
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