Artificial stabilization of the fusion pore by intra-organelle styrene–maleic acid copolymers

Caparotta, Marcelo; Puiatti, Marcelo; Masone, Diego

doi:10.1039/d1sm00978h

Cited by 4 publications

(3 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These bilayer patches of $17 Â 17 nm ensure negligible nite-size effects due to interactions between periodic images of the fusion pore. 5,56 In all cases, the pair of bilayers were solvated in more than $30 Â 10 3 W coarse-grained water molecules to fulll the ample water conditions for MARTINI. 57 The PO 4 :PO 4 inter-membrane separation was adjusted to equilibrate at $3.9 nm to t one and two Syt1-C2B domains.…”

Section: Methodsmentioning

confidence: 99%

Synaptotagmin-1 C2B domains cooperatively stabilize the fusion stalk via a master-servant mechanism

Bartolo

Masone

2022

Chem. Sci.

Self Cite

View full text Add to dashboard Cite

show abstract

Section: Methodsmentioning

confidence: 99%

Synaptotagmin-1 C2B domains cooperatively stabilize the fusion stalk via a master-servant mechanism

Bartolo

Masone

2022

Chem. Sci.

Self Cite

View full text Add to dashboard Cite

show abstract

“…In all cases, we have used a pair of lipid bilayers containing 1024 molecules each. These bilayer patches of ∼17 nm × 17 nm ensure negligible finite-size effects due to interactions between periodic images of the fusion pore. , The pair of bilayers were solvated in more than ∼30 × 10 3 W coarse-grained water molecules to fulfill the ample water condition for Martini . The intermembrane separation was adjusted to equilibrate at ∼3.9 nm to fit a Syt1-C2B domain.…”

Section: Computational Methodsmentioning

confidence: 99%

Enhanced Expansion and Reduced Kiss-and-Run Events in Fusion Pores Steered by Synaptotagmin-1 C2B Domains

Bartolo

Tomes

Mayorga

et al. 2022

J. Chem. Theory Comput.

Self Cite

View full text Add to dashboard Cite

The fusion pore controls the release of exocytotic vesicle contents through a precise orchestration of lipids from the fusing membranes and proteins. There is a major lipid reorganization during the different stages in life of the fusion pore (membrane fusion, nucleation, and expansion) that can be scrutinized thermodynamically. In this work, using umbrella sampling simulations we describe the expansion of the fusion pore. We have calculated free energy profiles to drive a nascent, just nucleated, fusion pore to its expanded configuration. We have quantified the effects on the free energy of one and two Synaptotagmin-1 C2B domains in the cytosolic space. We show that C2B domains cumulatively reduce the cost for expansion, favoring the system to evolve toward full fusion. Finally, by conducting thousands of unbiased molecular dynamics simulations, we show that C2B domains significantly decrease the probability of kiss-and-run events.

show abstract

“…However, the complete destruction of bilayer and formation of lipodiscs was not observed in that study, presumably due to the limitations of the simulation setup (application of the periodic boundary conditions). Another recent computational study supported the ability of SMA to stabilize transmembrane pores [ 78 ]. The pore-forming activity of SMA was also experimentally confirmed in [ 65 ] and [ 79 ].…”

Section: Formation Structure and Dynamics Of Lipodiscsmentioning

confidence: 97%

Mechanisms of Formation, Structure, and Dynamics of Lipoprotein Discs Stabilized by Amphiphilic Copolymers: A Comprehensive Review

et al. 2022

View full text Add to dashboard Cite

Amphiphilic copolymers consisting of alternating hydrophilic and hydrophobic units account for a major recent methodical breakthrough in the investigations of membrane proteins. Styrene–maleic acid (SMA), diisobutylene–maleic acid (DIBMA), and related copolymers have been shown to extract membrane proteins directly from lipid membranes without the need for classical detergents. Within the particular experimental setup, they form disc-shaped nanoparticles with a narrow size distribution, which serve as a suitable platform for diverse kinds of spectroscopy and other biophysical techniques that require relatively small, homogeneous, water-soluble particles of separate membrane proteins in their native lipid environment. In recent years, copolymer-encased nanolipoparticles have been proven as suitable protein carriers for various structural biology applications, including cryo-electron microscopy (cryo-EM), small-angle scattering, and conventional and single-molecule X-ray diffraction experiments. Here, we review the current understanding of how such nanolipoparticles are formed and organized at the molecular level with an emphasis on their chemical diversity and factors affecting their size and solubilization efficiency.

show abstract

Artificial stabilization of the fusion pore by intra-organelle styrene–maleic acid copolymers

Abstract: Styrene-maleic acid copolymers have become an advantageous detergent-free alternative for membrane protein isolation. Since their discovery, experimental membrane protein extraction and purification by keeping intact their lipid environment has become...

Cited by 4 publications

References 57 publications

Synaptotagmin-1 C2B domains cooperatively stabilize the fusion stalk via a master-servant mechanism

Synaptotagmin-1 C2B domains cooperatively stabilize the fusion stalk via a master-servant mechanism

Enhanced Expansion and Reduced Kiss-and-Run Events in Fusion Pores Steered by Synaptotagmin-1 C2B Domains

Mechanisms of Formation, Structure, and Dynamics of Lipoprotein Discs Stabilized by Amphiphilic Copolymers: A Comprehensive Review

Contact Info

Product

Resources

About