scholarly journals ORF3a of the COVID-19 virus SARS-CoV-2 blocks HOPS complex-mediated assembly of the SNARE complex required for autolysosome formation

2020 ◽  
Author(s):  
Guangyan Miao ◽  
Hongyu Zhao ◽  
Yan Li ◽  
Mingming Ji ◽  
Yong Chen ◽  
...  
Keyword(s):  
Snare Complex ◽  
Hops Complex

scholarly journals Yeast homotypic vacuole fusion requires the Ccz1–Mon1 complex during the tethering/docking stage

2003 ◽  
Vol 163 (5) ◽  
pp. 973-985 ◽  
Author(s):  
Chao-Wen Wang ◽  
Per E. Stromhaug ◽  
Emily J. Kauffman ◽  
Lois S. Weisman ◽  
Daniel J. Klionsky
Keyword(s):  
Protein Complex ◽  
Complex Interaction ◽  
Snare Complex ◽  
Morphological Evidence ◽  
Vacuole Membrane ◽  
Vacuole Fusion ◽  
Class C ◽  
Hops Complex

The function of the yeast lysosome/vacuole is critically linked with the morphology of the organelle. Accordingly, highly regulated processes control vacuolar fission and fusion events. Analysis of homotypic vacuole fusion demonstrated that vacuoles from strains defective in the CCZ1 and MON1 genes could not fuse. Morphological evidence suggested that these mutant vacuoles could not proceed to the tethering/docking stage. Ccz1 and Mon1 form a stable protein complex that binds the vacuole membrane. In the absence of the Ccz1–Mon1 complex, the integrity of vacuole SNARE pairing and the unpaired SNARE class C Vps/HOPS complex interaction were both impaired. The Ccz1–Mon1 complex colocalized with other fusion components on the vacuole as part of the cis-SNARE complex, and the association of the Ccz1–Mon1 complex with the vacuole appeared to be regulated by the class C Vps/HOPS complex proteins. Accordingly, we propose that the Ccz1–Mon1 complex is critical for the Ypt7-dependent tethering/docking stage leading to the formation of a trans-SNARE complex and subsequent vacuole fusion.

scholarly journals Membrane Fusion can be Driven by Sec18/NSF, Sec17/αSNAP, and trans-SNARE complex without HOPS

2021 ◽  
Author(s):  
William T Wickner ◽  
Hongki Song
Keyword(s):  
Membrane Fusion ◽  
Vacuolar Membrane ◽  
Snare Complex ◽  
Direct Result ◽  
General Role ◽  
Endocytic Traffic ◽  
Hops Complex ◽  
Tethered Membranes

Yeast vacuolar membrane fusion has been reconstituted with R, Qa, Qb, and Qc-family SNAREs, Sec17/αSNAP, Sec18/NSF, and the hexameric HOPS complex. HOPS tethers membranes and catalyzes SNARE assembly into RQaQbQc trans-complexes which zipper through their SNARE domains to promote fusion. Previously, we demonstrated that Sec17 and Sec18 can bypass the requirement of complete zippering for fusion (Song et al., 2021), but it has been unclear whether this activity of Sec17 and Sec18 is directly coupled to HOPS. HOPS can be replaced for fusion by a synthetic tether when the three Q-SNAREs are pre-assembled. We now report that SNARE zippering-arrested fusion intermediates that are formed without HOPS support Sec17/Sec18-triggered fusion. This zippering-bypass fusion is thus a direct result of Sec17 and Sec18 interactions: with each other, with the platform of partially zippered SNAREs, and with the apposed tethered membranes. As these fusion elements are shared among all exocytic and endocytic traffic, Sec17 and Sec18 may have a general role in directly promoting fusion.

scholarly journals Phosphatidylinositol and phosphatidylinositol-3-phosphate activate HOPS to catalyze SNARE assembly, allowing small headgroup lipids to support the terminal steps of membrane fusion

2021 ◽  
pp. mbc.E21-04-0191
Author(s):  
Thomas Torng ◽  
William Wickner
Keyword(s):  
Phosphatidic Acid ◽  
Membrane Fusion ◽  
Snare Complex ◽  
Rab Gtpases ◽  
Intracellular Membrane ◽  
Complex Assembly ◽  
Membrane Tethering ◽  
Intracellular Membrane Fusion ◽  
Phosphatidylinositol 3 ◽  
Hops Complex

Intracellular membrane fusion requires Rab GTPases, tethers, SNAREs of the R, Qa, Qb, and Qc families, and SNARE chaperones of the Sec17 (SNAP), Sec18 (NSF), and SM (Sec1/Munc18) families. The vacuolar HOPS complex combines the functions of membrane tethering and SM catalysis of SNARE assembly. HOPS is activated for this catalysis by binding to the vacuolar lipids and Rab. Of the 8 major vacuolar lipids, we now report that phosphatidylinositol and phosphatidylinositol-3-phosphate are required to activate HOPS for SNARE complex assembly. These lipids plus ergosterol also allow full trans-SNARE complex assembly, yet do not support fusion, which is reliant on either phosphatidylethanolamine (PE) or on phosphatidic acid (PA), phosphatidylserine (PS), and diacylglycerol (DAG). Fusion with a synthetic tether and without HOPS, or even without SNAREs, still relies on either PE or on PS, PA, and DAG. These lipids are thus required for the terminal bilayer rearrangement step of fusion, distinct from the lipid requirements for the earlier step of activating HOPS for trans-SNARE assembly.

scholarly journals The N-terminal Domain of the t-SNARE Vam3p Coordinates Priming and Docking in Yeast Vacuole Fusion

2001 ◽  
Vol 12 (11) ◽  
pp. 3375-3385 ◽  
Author(s):  
Rico Laage ◽  
Christian Ungermann
Keyword(s):  
Membrane Fusion ◽  
Terminal Region ◽  
Snare Complex ◽  
Truncated Protein ◽  
Sequence Of Events ◽  
Vacuole Fusion ◽  
N Terminus ◽  
Hops Complex

Homotypic fusion of yeast vacuoles requires a regulated sequence of events. During priming, Sec18p disassembles cis-SNARE complexes. The HOPS complex, which is initially associated with thecis-SNARE complex, then mediates tethering. Finally, SNAREs assemble into trans-complexes before the membranes fuse. The t-SNARE of the vacuole, Vam3p, plays a central role in the coordination of these processes. We deleted the N-terminal region of Vam3p to analyze the role of this domain in membrane fusion. The truncated protein (Vam3ΔN) is sorted normally to the vacuole and is functional, because the vacuolar morphology is unaltered in this strain. However, in vitro vacuole fusion is strongly reduced due to the following reasons: Assembly, as well as disassembly of thecis-SNARE complex is more efficient on Vam3ΔN vacuoles; however, the HOPS complex is not associated well with the Vam3ΔN cis-complex. Thus, primed SNAREs from Vam3ΔN vacuoles cannot participate efficiently in the reaction becausetrans-SNARE pairing is substantially reduced. We conclude that the N-terminus of Vam3p is required for coordination of priming and docking during homotypic vacuole fusion.

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