{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Duan M"],"funding":["University of Washington","Medical Research Council","National Institutes of Health","National Institute of General Medical Sciences","NIGMS NIH HHS","NIH HHS"],"pagination":["e202001032"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10943277"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["223(6)"],"pubmed_abstract":["The essential Golgi protein Sly1 is a member of the Sec1/mammalian Unc-18 (SM) family of SNARE chaperones. Sly1 was originally identified through remarkable gain-of-function alleles that bypass requirements for diverse vesicle tethering factors. Employing genetic analyses and chemically defined reconstitutions of ER-Golgi fusion, we discovered that a loop conserved among Sly1 family members is not only autoinhibitory but also acts as a positive effector. An amphipathic lipid packing sensor (ALPS)-like helix within the loop directly binds high-curvature membranes. Membrane binding is required for relief of Sly1 autoinhibition and also allows Sly1 to directly tether incoming vesicles to the Qa-SNARE on the target organelle. The SLY1-20 mutation bypasses requirements for diverse tethering factors but loses this ability if the tethering activity is impaired. We propose that long-range tethers, including Golgins and multisubunit tethering complexes, hand off vesicles to Sly1, which then tethers at close range to initiate trans-SNARE complex assembly and fusion in the early secretory pathway."],"journal":["The Journal of cell biology"],"pubmed_title":["SNARE chaperone Sly1 directly mediates close-range vesicle tethering."],"pmcid":["PMC10943277"],"funding_grant_id":["R01 GM130644","T34 GM083883","MC_UP_1201/10","R01 GM077349","T32 GM007270"],"pubmed_authors":["Nattermann U","Lin A","Duan M","Miller EA","Mima J","Plemel RL","Delgado BM","Takenaka T","Nickerson DP","Merz AJ"],"additional_accession":[]},"is_claimable":false,"name":"SNARE chaperone Sly1 directly mediates close-range vesicle tethering.","description":"The essential Golgi protein Sly1 is a member of the Sec1/mammalian Unc-18 (SM) family of SNARE chaperones. Sly1 was originally identified through remarkable gain-of-function alleles that bypass requirements for diverse vesicle tethering factors. Employing genetic analyses and chemically defined reconstitutions of ER-Golgi fusion, we discovered that a loop conserved among Sly1 family members is not only autoinhibitory but also acts as a positive effector. An amphipathic lipid packing sensor (ALPS)-like helix within the loop directly binds high-curvature membranes. Membrane binding is required for relief of Sly1 autoinhibition and also allows Sly1 to directly tether incoming vesicles to the Qa-SNARE on the target organelle. The SLY1-20 mutation bypasses requirements for diverse tethering factors but loses this ability if the tethering activity is impaired. We propose that long-range tethers, including Golgins and multisubunit tethering complexes, hand off vesicles to Sly1, which then tethers at close range to initiate trans-SNARE complex assembly and fusion in the early secretory pathway.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Jun","modification":"2026-06-01T16:31:50.618Z","creation":"2025-04-06T19:30:03.813Z"},"accession":"S-EPMC10943277","cross_references":{"pubmed":["38478018"],"doi":["10.1083/jcb.202001032"]}}