| First Author | Shaaban A | Year | 2019 |
| Journal | Elife | Volume | 8 |
| PubMed ID | 30883328 | Mgi Jnum | J:275211 |
| Mgi Id | MGI:6304229 | Doi | 10.7554/eLife.41720 |
| Citation | Shaaban A, et al. (2019) The SNAP-25 linker supports fusion intermediates by local lipid interactions. Elife 8:e41720 |
| abstractText | SNAP-25 is an essential component of SNARE complexes driving fast Ca(2+)-dependent exocytosis. Yet, the functional implications of the tandem-like structure of SNAP-25 are unclear. Here, we have investigated the mechanistic role of the acylated "linker" domain that concatenates the two SNARE motifs within SNAP-25. Refuting older concepts of an inert connector, our detailed structure-function analysis in murine chromaffin cells demonstrates that linker motifs play a crucial role in vesicle priming, triggering, and fusion pore expansion. Mechanistically, we identify two synergistic functions of the SNAP-25 linker: First, linker motifs support t-SNARE interactions and accelerate ternary complex assembly. Second, the acylated N-terminal linker segment engages in local lipid interactions that facilitate fusion triggering and pore evolution, putatively establishing a favorable membrane configuration by shielding phospholipid headgroups and affecting curvature. Hence, the linker is a functional part of the fusion complex that promotes secretion by SNARE interactions as well as concerted lipid interplay. |
