Syntaxin N-terminal peptide motif is an initiation factor for the assembly of the SNARE–Sec1/Munc18 membrane fusion complex

DOI Web Site 被引用文献1件
  • Shailendra S. Rathore
    Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309; and
  • Eric G. Bend
    The Howard Hughes Medical Institute, Department of Biology, University of Utah, Salt Lake City, UT 84112
  • Haijia Yu
    Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309; and
  • Marc Hammarlund
    The Howard Hughes Medical Institute, Department of Biology, University of Utah, Salt Lake City, UT 84112
  • Erik M. Jorgensen
    The Howard Hughes Medical Institute, Department of Biology, University of Utah, Salt Lake City, UT 84112
  • Jingshi Shen
    Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309; and

説明

<jats:p>Intracellular membrane fusion is mediated by the concerted action of<jats:italic>N</jats:italic>-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) and Sec1/Munc18 (SM) proteins. During fusion, SM proteins bind the N-terminal peptide (N-peptide) motif of the SNARE subunit syntaxin, but the function of this interaction is unknown. Here, using FRET-based biochemical reconstitution and<jats:italic>Caenorhabditis elegans</jats:italic>genetics, we show that the N-peptide of syntaxin-1 recruits the SM protein Munc18-1/nSec1 to the SNARE bundle, facilitating their assembly into a fusion-competent complex. The recruitment is achieved through physical tethering rather than allosteric activation of Munc18-1. Consistent with the recruitment role, the N-peptide is not spatially constrained along syntaxin-1, and it is functional when translocated to another SNARE subunit SNAP-25 or even when simply anchored in the target membrane. The N-peptide function is restricted to an early initiation stage of the fusion reaction. After association, Munc18-1 and the SNARE bundle together drive membrane merging without further involving the N-peptide. Thus, the syntaxin N-peptide is an initiation factor for the assembly of the SNARE-SM membrane fusion complex.</jats:p>

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