scholarly journals Liposome fusion with orthogonal coiled-coil peptides as fusogens: The efficacy of roleplaying peptides

2021 ◽  
Author(s):  
Geert G.A. Daudey ◽  
Meng-Jie Shen ◽  
Ankush Singhal ◽  
Patrick Van der Est ◽  
Agur Sevink ◽  
...  
Keyword(s):  
Membrane Fusion ◽  
Biological Membrane ◽  
Coiled Coil ◽  
Complex Environment ◽  
Target Delivery ◽  
Liposome Fusion

Biological membrane fusion is a highly specific and coordinated process as a multitude of vesicular fusion events proceed simultaneously in a complex environment with minimal off-target delivery. In this study,...

scholarly journals Synaptotagmin-1 C2B domain interacts simultaneously with SNAREs and membranes to promote membrane fusion

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Shen Wang ◽  
Yun Li ◽  
Cong Ma
Keyword(s):  
Membrane Fusion ◽  
Neurotransmitter Release ◽  
Functional Significance ◽  
Underlying Mechanism ◽  
C2 Domains ◽  
Membrane Deformation ◽  
Synaptotagmin 1 ◽  
Bottom Face ◽  
Liposome Fusion

Synaptotagmin-1 (Syt1) acts as a Ca2+ sensor for neurotransmitter release through its C2 domains. It has been proposed that Syt1 promotes SNARE-dependent fusion mainly through its C2B domain, but the underlying mechanism is poorly understood. In this study, we show that the C2B domain interacts simultaneously with acidic membranes and SNARE complexes via the top Ca2+-binding loops, the side polybasic patch, and the bottom face in response to Ca2+. Disruption of the simultaneous interactions completely abrogates the triggering activity of the C2B domain in liposome fusion. We hypothesize that the simultaneous interactions endow the C2B domain with an ability to deform local membranes, and this membrane-deformation activity might underlie the functional significance of the Syt1 C2B domain in vivo.

scholarly journals Membrane lysis during biological membrane fusion: collateral damage by misregulated fusion machines

2008 ◽  
Vol 183 (2) ◽  
pp. 181-186 ◽  
Author(s):  
Alex Engel ◽  
Peter Walter
Keyword(s):  
Membrane Fusion ◽  
Biological Membrane ◽  
Membrane Integrity ◽  
Fusion Pore ◽  
Mechanistic Models ◽  
Collateral Damage ◽  
Vacuole Fusion ◽  
Membrane Lysis

In the canonical model of membrane fusion, the integrity of the fusing membranes is never compromised, preserving the identity of fusing compartments. However, recent molecular simulations provided evidence for a pathway to fusion in which holes in the membrane evolve into a fusion pore. Additionally, two biological membrane fusion models—yeast cell mating and in vitro vacuole fusion—have shown that modifying the composition or altering the relative expression levels of membrane fusion complexes can result in membrane lysis. The convergence of these findings showing membrane integrity loss during biological membrane fusion suggests new mechanistic models for membrane fusion and the role of membrane fusion complexes.

Lipids in biological membrane fusion

1995 ◽  
Vol 146 (1) ◽  
Author(s):  
L. Chernomordik ◽  
M.M. Kozlov ◽  
J. Zimmerberg
Keyword(s):  
Membrane Fusion ◽  
Biological Membrane

scholarly journals Coiled-coil formation of the membrane-fusion K/E peptides viewed by electron paramagnetic resonance

PLoS ONE ◽  
2018 ◽  
Vol 13 (1) ◽  
pp. e0191197 ◽  
Author(s):  
Pravin Kumar ◽  
Martin van Son ◽  
Tingting Zheng ◽  
Dayenne Valdink ◽  
Jan Raap ◽  
...  
Keyword(s):  
Electron Paramagnetic Resonance ◽  
Membrane Fusion ◽  
Coiled Coil ◽  
Paramagnetic Resonance ◽  
Electron Paramagnetic

scholarly journals Coassembly of Mgm1 isoforms requires cardiolipin and mediates mitochondrial inner membrane fusion

2009 ◽  
Vol 186 (6) ◽  
pp. 793-803 ◽  
Author(s):  
Rachel M. DeVay ◽  
Lenin Dominguez-Ramirez ◽  
Laura L. Lackner ◽  
Suzanne Hoppins ◽  
Henning Stahlberg ◽  
...  
Keyword(s):  
Membrane Fusion ◽  
Coiled Coil ◽  
Intermembrane Space ◽  
Dependent Manner ◽  
Related Protein ◽  
Mitochondrial Membranes ◽  
Inner Membrane ◽  
Mitochondrial Inner Membrane ◽  
N Terminus ◽  
In Trans

Two dynamin-related protein (DRP) families are essential for fusion of the outer and inner mitochondrial membranes, Fzo1 (yeast)/Mfn1/Mfn2 (mammals) and Mgm1 (yeast)/Opa1 (mammals), respectively. Fzo1/Mfns possess two medial transmembrane domains, which place their critical GTPase and coiled-coil domains in the cytosol. In contrast, Mgm1/Opa1 are present in cells as long (l) isoforms that are anchored via the N terminus to the inner membrane, and short (s) isoforms were predicted to be soluble in the intermembrane space. We addressed the roles of Mgm1 isoforms and how DRPs function in membrane fusion. Our analysis indicates that in the absence of a membrane, l- and s-Mgm1 both exist as inactive GTPase monomers, but that together in trans they form a functional dimer in a cardiolipin-dependent manner that is the building block for higher-order assemblies.

scholarly journals Expansion of the fusion stalk and its implication for biological membrane fusion

2014 ◽  
Vol 111 (30) ◽  
pp. 11043-11048 ◽  
Author(s):  
H. J. Risselada ◽  
G. Bubnis ◽  
H. Grubmuller
Keyword(s):  
Membrane Fusion ◽  
Biological Membrane

Coiled coil driven membrane fusion between cyclodextrin vesicles and liposomes

Soft Matter ◽  
2014 ◽  
Vol 10 (48) ◽  
pp. 9746-9751 ◽  
Author(s):  
Frank Versluis ◽  
Jens Voskuhl ◽  
Jan Vos ◽  
Heiner Friedrich ◽  
Bart Jan Ravoo ◽  
...  
Keyword(s):  
Membrane Fusion ◽  
Coiled Coil

scholarly journals Nonhelical Leash and α-Helical Structures Determine the Potency of a Peptide Antagonist of Human T-Cell Leukemia Virus Entry

2008 ◽  
Vol 82 (10) ◽  
pp. 4965-4973 ◽  
Author(s):  
Antonis Mirsaliotis ◽  
Daniel Lamb ◽  
David W. Brighty
Keyword(s):  
Amino Acid ◽  
T Cell ◽  
Membrane Fusion ◽  
Fusion Proteins ◽  
Leukemia Virus ◽  
Coiled Coil ◽  
Cell Leukemia ◽  
Inhibitory Peptide ◽  
Human T Cell ◽  
T Cell Leukemia Virus

ABSTRACT Viral fusion proteins mediate the entry of enveloped viral particles into cells by inducing fusion of the viral and target cell membranes. Activated fusion proteins undergo a cascade of conformational transitions and ultimately resolve into a compact trimer of hairpins or six-helix bundle structure, which pulls the interacting membranes together to promote lipid mixing. Significantly, synthetic peptides based on a C-terminal region of the trimer of hairpins are potent inhibitors of membrane fusion and viral entry, and such peptides are typically extensively α-helical. In contrast, an atypical peptide inhibitor of human T-cell leukemia virus (HTLV) includes α-helical and nonhelical leash segments. We demonstrate that both the C helix and C-terminal leash are critical to the inhibitory activities of these peptides. Amino acid side chains in the leash and C helix extend into deep hydrophobic pockets at the membrane-proximal end of the HTLV type 1 (HTLV-1) coiled coil, and these contacts are necessary for potent antagonism of membrane fusion. In addition, a single amino acid substitution within the inhibitory peptide improves peptide interaction with the core coiled coil and yields a peptide with enhanced potency. We suggest that the deep pockets on the coiled coil are ideal targets for small-molecule inhibitors of HTLV-1 entry into cells. Moreover, the extended nature of the HTLV-1-inhibitory peptide suggests that such peptides may be intrinsically amenable to modifications designed to improve inhibitory activity. Finally, we propose that leash-like mimetic peptides may be of value as entry inhibitors for other clinically important viral infections.

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