Structural Analysis of the Neuronal SNARE Protein Syntaxin-1A † , ‡

Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA.
Biochemistry (Impact Factor: 3.02). 08/2000; 39(29):8470-9. DOI: 10.1021/bi0003994
Source: PubMed


Intracellular trafficking depends on the docking and fusion of transport vesicles with cellular membranes. Central to docking and fusion is the pairing of SNARE proteins (soluble NSF attachment protein receptors) associated with the vesicle and target membranes (v- and t-SNAREs, respectively). Here, the X-ray structure of an N-terminal conserved domain of the neuronal t-SNARE syntaxin-1A was determined to a resolution of 1.9 A using multiwavelength anomalous diffraction. This X-ray structure, which is in general agreement with an NMR structure of a similar fragment, provides new insight into the interaction surface between the N-terminal domain and the remainder of the protein. In vitro characterization of the intact cytoplasmic domain of syntaxin revealed that it forms dimers, and probably tetramers, at low micromolar concentrations, with concomitant structural changes that can be detected by limited proteolysis. These observations suggest that the promiscuity characteristic of pairing between v-SNAREs and t-SNAREs extends to the formation of homo-oligomeric t-SNARE complexes as well. They also suggest a potential role for the neuronal Sec1 protein (nSec1) in preventing the formation of syntaxin multimers.

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Available from: Robert Fairman, Jul 15, 2015
    • "The membrane target SNARE (tSNARE) syntaxin 1A is composed of a N-terminal three-helix bundle H abc , an amphipathic helix H 3 that interacts with other SNARE proteins to form a fusion complex (or the H abc domain), and a C-terminal TM domain [104] [105] [106] [107] "
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    • "Opening of the Stx1 structure is at least in part mediated by Munc13-1 (Ma et al., 2011), a large protein that is structurally homologous to CATCHR-type tethering factor subunits (Li et al., 2011). This conformational change depends on interactions of the CATCHR-fold MUN domain of Munc13-1 with both the Stx1 SNARE motif and Munc18-1 (Ma et al., 2011; Lerman et al., 2000). Several considerations suggest that this model may not apply to the Stx6-Ang2 interaction characterized in our study. "
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    • "This structure, denoted Habc, may fold back onto the SNARE domain and enable the molecule to adopt a 'closed' conformation that prevents assembly of the core fusion complex (i.e. Habc could act as an autoinhibitor of SNARE function) (Lerman et al., 2000; Teng et al., 2001). A second type of autonomous N-terminal structure, a profilin-like domain, is present within some R-SNAREs as well as putatively unrelated proteins (Rossi et al., 2004). "
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