RT Journal Article
SR Electronic
T1 Gatekeeper helix activates Golgi SM protein Sly1 and directly mediates close-range vesicle tethering
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.01.16.906719
DO 10.1101/2020.01.16.906719
A1 M. Duan
A1 R.L. Plemel
A1 T. Takenaka
A1 A. Lin
A1 B.M. Delgado
A1 U. Nattermann
A1 D.P. Nickerson
A1 J. Mima
A1 E.A. Miller
A1 A.J. Merz
YR 2020
UL http://biorxiv.org/content/early/2020/01/16/2020.01.16.906719.abstract
AB The essential Golgi protein Sly1 is a member of the SM (Sec1/mammalian Unc-18) family of SNARE chaperones. Sly1 was originally identified through 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 helix within the loop directly binds high-curvature membranes; membrane binding is required for relief of Sly1 autoinhibition and allows Sly1 to directly tether incoming vesicles to the Qa-SNARE on the target organelle. The SLY1-20 allele bypasses requirements for diverse tethering factors but loses this functionality if Sly1 membrane binding 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 activate SNARE assembly and fusion in the early secretory pathway.