AI Article Synopsis
- Sly1 and SNARE proteins, such as Sed5, play crucial roles in membrane fusion by acting as cofactors, and the study investigates how Sly1 enhances this process through various mechanisms.
- Three mechanisms were identified: Sly1 helps to open Sed5's closed conformation, tethers vesicles close to target organelles, and supports the formation of trans-SNARE complexes, all working in parallel to facilitate membrane fusion.
- The N-terminal Habc domain of Sed5 has two key functions: it ensures proper localization of Sed5 and promotes fusion, while a version of Sed5 without the Habc domain can still support fusion activities in both lab and living cells, indicating that Habc
Article Abstract
SM proteins including Sly1 are essential cofactors of SNARE-mediated membrane fusion. Using SNARE and Sly1 mutants and chemically defined in vitro assays, we separate and assess proposed mechanisms through which Sly1 augments fusion: (i) opening the closed conformation of the Qa-SNARE Sed5; (ii) close-range tethering of vesicles to target organelles, mediated by the Sly1-specific regulatory loop; and (iii) nucleation of productive trans-SNARE complexes. We show that all three mechanisms are important and operate in parallel, and that close-range tethering promotes trans-complex assembly when cis-SNARE assembly is a competing process. Further, we demonstrate that the autoinhibitory N-terminal Habc domain of Sed5 has at least two positive activities: it is needed for correct Sed5 localization, and it directly promotes Sly1-dependent fusion. "Split Sed5," with Habc presented solely as a soluble fragment, can function both in vitro and in vivo. Habc appears to facilitate events leading to lipid mixing rather than promoting opening or stability of the fusion pore.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10943372 | PMC |
| http://dx.doi.org/10.1083/jcb.202001034 | DOI Listing |
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Article Synopsis
- Sly1 and SNARE proteins, such as Sed5, play crucial roles in membrane fusion by acting as cofactors, and the study investigates how Sly1 enhances this process through various mechanisms.
- Three mechanisms were identified: Sly1 helps to open Sed5's closed conformation, tethers vesicles close to target organelles, and supports the formation of trans-SNARE complexes, all working in parallel to facilitate membrane fusion.
- The N-terminal Habc domain of Sed5 has two key functions: it ensures proper localization of Sed5 and promotes fusion, while a version of Sed5 without the Habc domain can still support fusion activities in both lab and living cells, indicating that Habc
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