scholarly journals Dual role of a GTPase conformational switch for membrane fusion by mitofusin ubiquitylation

2019 ◽  
Vol 3 (1) ◽  
pp. e201900476 ◽  
Author(s):  
Ramona Schuster ◽  
Vincent Anton ◽  
Tânia Simões ◽  
Selver Altin ◽  
Fabian den Brave ◽  
...  
Keyword(s):  
Membrane Fusion ◽  
Posttranslational Modifications ◽  
Dual Role ◽  
Dynamic Nature ◽  
Gtpase Domain ◽  
Dynamic Changes ◽  
Conformational Switch ◽  
Outer Membranes ◽  
Large Gtpases

Mitochondria are essential organelles whose function is upheld by their dynamic nature. This plasticity is mediated by large dynamin-related GTPases, called mitofusins in the case of fusion between two mitochondrial outer membranes. Fusion requires ubiquitylation, attached to K398 in the yeast mitofusin Fzo1, occurring in atypical and conserved forms. Here, modelling located ubiquitylation to α4 of the GTPase domain, a critical helix in Ras-mediated events. Structure-driven analysis revealed a dual role of K398. First, it is required for GTP-dependent dynamic changes of α4. Indeed, mutations designed to restore the conformational switch, in the absence of K398, rescued wild-type-like ubiquitylation on Fzo1 and allowed fusion. Second, K398 is needed for Fzo1 recognition by the pro-fusion factors Cdc48 and Ubp2. Finally, the atypical ubiquitylation pattern is stringently required bilaterally on both involved mitochondria. In contrast, exchange of the conserved pattern with conventional ubiquitin chains was not sufficient for fusion. In sum, α4 lysines from both small and large GTPases could generally have an electrostatic function for membrane interaction, followed by posttranslational modifications, thus driving membrane fusion events.

Dynamic changes in plasma membrane properties of semliki forest virus infected cells related to cell fusion

1988 ◽  
Vol 8 (3) ◽  
pp. 241-254 ◽  
Author(s):  
C. Kempf ◽  
M. R. Michel ◽  
U. Kohler ◽  
H. Koblet ◽  
H. Oetliker
Keyword(s):  
Plasma Membrane ◽  
Membrane Potential ◽  
Membrane Fusion ◽  
Cell Fusion ◽  
Semliki Forest Virus ◽  
Membrane Properties ◽  
Acidic Ph ◽  
Dynamic Changes ◽  
Infected Cells

The mechanism of the processes leading to membrane fusion is as yet unknown. In this report we demonstrate that changes in membrane potential and potassium fluxes correlate with Semliki Forest virus induced cell-cell fusion at mildly acidic pH. The changes observed occur only at pH's below 6.2 corresponding to values required to trigger the fusion process. A possible role of these alterations of the plasma membrane related to membrane fusion phenomena is discussed.

scholarly journals Mfn2 requires Hinge 1 integrity for efficient nucleotide-dependent assembly and membrane fusion

2019 ◽  
Author(s):  
N.B. Samanas ◽  
E.A. Engelhart ◽  
S. Hoppins
Keyword(s):  
Membrane Fusion ◽  
Conformational Changes ◽  
Wild Type ◽  
Structural Domains ◽  
Nucleotide Hydrolysis ◽  
Helical Bundles ◽  
Trans Complex ◽  
Large Gtpases

ABSTRACTMitofusins are members of the dynamin-related protein family, large GTPases that harness the energy from nucleotide hydrolysis to remodel membranes. Mitofusins possess four structural domains including two extended helical bundles that are connected by a flexible linker. The role of this linker (Hinge 1) in mitofusin-mediated membrane fusion is not well understood. We have characterized four variants with amino acid substitutions within this region of Mfn2. While a defect was not apparent in cells, a fusion deficiency was observed in vitro, and was rescued by the addition of cytosolic fraction. All four variants had decreased nucleotide-dependent assembly, which was improved by the addition of Bax. Assembly of mitofusins across two membranes was unaffected as formation of the trans complex was similar to wild type for all variants. We further demonstrate that variants with substitutions in both helical bundles are more severely impaired than any single mutant, suggesting that both helical bundles contribute to this function. Our data are consistent with a model where this region contributes to conformational changes that are important for assembly.

scholarly journals Cryo-EM structures reveal a conformational change of SOPA1 during mitochondrial inner membrane fusion

2019 ◽  
Author(s):  
Danyang Zhang ◽  
Yan Zhang ◽  
Jun Ma ◽  
Tongxin Niu ◽  
Wenbo Chen ◽  
...  
Keyword(s):  
Membrane Fusion ◽  
Bound States ◽  
General Structure ◽  
Proteolytic Processing ◽  
Gtpase Domain ◽  
Inner Membrane ◽  
Unique Role ◽  
Mitochondrial Inner Membrane ◽  
Membrane Tubulation

ABSTRACTMammalian mitochondrial inner membrane fusion is mediated by OPA1(optic atrophy 1). Under physiological condition, OPA1 undergoes proteolytic processing to form a membrane-anchored long isoform (LOPA1) and a soluble short isoform (SOPA1). A combination of LOPA1 and SOPA1 are required for membrane fusion, however, the relevant mechanism is not well understood. In this study, we investigate the cryo-EM structures of SOPA1 coated liposome tube at nucleotide-free and GTPγS bound states. SOPA1 exhibits a general structure of dynamin family and can assemble onto membrane in a helical array with a building block of dimer and thus induce membrane tubulation. A predicted amphipathic helix is discovered to mediate the tubulation activity of SOPA1. The binding of GTPγS causes a conformational rotation between GTPase domain and stalk region, and then induces a rearrangement of the helical array and an expansion of the tube, which is opposite to the behavior of other dynamin proteins, suggesting a unique role of SOPA1 in the fusion of mitochondrial inner membrane.

Dual role of B7 costimulation in obesity-related non-alcoholic steatohepatitis (NASH) and metabolic dysregulation

2014 ◽  
Vol 122 (03) ◽  
Author(s):  
A Chatzigeorgiou ◽  
R Garcia-Martin ◽  
KJ Chung ◽  
I Alexaki ◽  
A Klotzsche-von Ameln ◽  
...  
Keyword(s):  
Dual Role ◽  
Alcoholic Steatohepatitis ◽  
Metabolic Dysregulation

A dual role of the N-terminal FQQI motif in GLUT4 trafficking

2008 ◽  
Vol 3 (S 1) ◽  
Author(s):  
U Bernhardt ◽  
HG Joost ◽  
H Al-Hasani
Keyword(s):  
Dual Role

Can trust become a factor of economic growth? Dynamic changes in the level of trust of Russian youth

2020 ◽  
pp. 92-107 ◽  
Author(s):  
A. I. Bakhtigaraeva ◽  
A. A. Stavinskaya
Keyword(s):  
Institutional Environment ◽  
Negative Effects ◽  
Dynamic Changes ◽  
Generalized Trust ◽  
Level Of Education ◽  
Advantages And Disadvantages ◽  
The Future ◽  
Analysis Of Dynamics

The article considers the role of trust in the economy, the mechanisms of its accumulation and the possibility of using it as one of the growth factors in the future. The advantages and disadvantages of measuring the level of generalized trust using two alternative questions — about trusting people in general and trusting strangers — are analyzed. The results of the analysis of dynamics of the level of generalized trust among Russian youth, obtained within the study of the Institute for National Projects in 10 regions of Russia, are presented. It is shown that there are no significant changes in trust in people in general during the study at university. At the same time, the level of trust in strangers falls, which can negatively affect the level of trust in the country as a whole, and as a result have negative effects on the development of the economy in the future. Possible causes of the observed trends and the role of universities are discussed. Also the question about the connection between the level of education and generalized trust in countries with different quality of the institutional environment is raised.

Dual Role of RKIP in NF-kB Signaling Pathways

2011 ◽  
Vol 2 (1) ◽  
pp. 21-34
Author(s):  
Huihui Tang ◽  
Sungdae Park ◽  
Kam C. Yeung
Keyword(s):  
Signaling Pathways ◽  
Dual Role
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