SNARE Modulators and SNARE Mimetic Peptides

Khvotchev, Mikhail; Soloviev, Mikhail

doi:10.3390/biom12121779

Cited by 8 publications

(5 citation statements)

References 138 publications

(147 reference statements)

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“…The implication of coiled-coil motifs in this study is not surprising, since these motifs are known to play a role in many other structures interacting with membranes such as in the SNARE complex [34]. In addition, successful examples in the design of membrane systems used coiled-coil motifs as a starting point.…”

Section: Discussionmentioning

confidence: 72%

Conformational Space of the Translocation Domain of Botulinum Toxin: Atomistic Modeling and Mesoscopic Description of the Coiled-Coil Helix Bundle

Delort,

Cottone,

Malliavin

et al. 2024

Preprint

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The toxicity of botulinum multi-domain neurotoxins (BoNTs) arises from a sequence of molecular events, in which the translocation of the catalytic domain through the membrane of a neurotransmitter vesicle plays a key role. A structural study (Lamet al., Nat. Comm., 2018) of the translocation domain of BoNT suggests that the interaction with the membrane is driven by the transition of anαhelical switch towards aβhairpin. Atomistic simulations in conjunction with the mesoscopicTwistermodel are used to investigate the consequences of this proposition for the toxin-membrane interaction. The conformational mobilities of the domain as well as the effect of the membrane, implicitly examined by comparing water and water-ethanol solvents, lead to the conclusion that the transition of the switch modifies the internal dynamics and the effect of membrane hydrophobicity on the whole protein. The central twoαhelices, helix 1 and helix 2, forming two coiled-coil motifs, are analyzed using theTwistermodel, in which the initial deformation of the membrane by the protein is caused by the presence of local torques arising from asymmetric positions of hydrophobic residues. Different torque distributions are observed depending on the switch conformations and permit to propose an origin for the mechanism opening the membrane.

show abstract

Section: Discussionmentioning

confidence: 72%

Conformational Space of the Translocation Domain of Botulinum Toxin: Atomistic Modeling and Mesoscopic Description of the Coiled-Coil Helix Bundle

Delort,

Cottone,

Malliavin

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…The implication of coiled-coil motifs in this study is not surprising, since these motifs are known to play a role in many other structures interacting with membranes, such as in the SNARE complex [ 35 ]. In addition, successful examples in the design of membrane systems used coiled-coil motifs as a starting point.…”

Section: Discussionmentioning

confidence: 88%

Conformational Space of the Translocation Domain of Botulinum Toxin: Atomistic Modeling and Mesoscopic Description of the Coiled-Coil Helix Bundle

Delort,

Cottone,

Malliavin

et al. 2024

IJMS

View full text Add to dashboard Cite

The toxicity of botulinum multi-domain neurotoxins (BoNTs) arises from a sequence of molecular events, in which the translocation of the catalytic domain through the membrane of a neurotransmitter vesicle plays a key role. A recent structural study of the translocation domain of BoNTs suggests that the interaction with the membrane is driven by the transition of an α helical switch towards a β hairpin. Atomistic simulations in conjunction with the mesoscopic Twister model are used to investigate the consequences of this proposition for the toxin–membrane interaction. The conformational mobilities of the domain, as well as the effect of the membrane, implicitly examined by comparing water and water–ethanol solvents, lead to the conclusion that the transition of the switch modifies the internal dynamics and the effect of membrane hydrophobicity on the whole protein. The central two α helices, helix 1 and helix 2, forming two coiled-coil motifs, are analyzed using the Twister model, in which the initial deformation of the membrane by the protein is caused by the presence of local torques arising from asymmetric positions of hydrophobic residues. Different torque distributions are observed depending on the switch conformations and permit an origin for the mechanism opening the membrane to be proposed.

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“…It is interesting to note in this context that the SNARE reaction has inspired the development of synthetic fusion machines. Among other things, DNA strands have been attached to membrane anchors and inserted into the membrane of liposomes (Khvotchev & Soloviev 2022; Paez-Perez et al 2022; Sadek et al 2016; Seeman & Sleiman 2017). They then interact with the complementary DNA strands in another liposome to fuse the membranes.…”

Section: Discussionmentioning

confidence: 99%

A look beyond the QR code of SNARE proteins

Yadav,

Hacisuleyman,

Dergai

et al. 2024

Preprint

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Soluble N-ethylmaleimide-sensitive factor Attachment protein REceptor (SNARE) proteins catalyze the fusion process of vesicles with target membranes in eukaryotic cells. To do this, they assemble in a zipper-like fashion into stable complexes between the membranes. Structural studies have shown that the complexes consist of four different helices, which we subdivide into Qa-, Qb-, Qc-, and R-helix on the basis of their sequence signatures. Using a combination of biochemistry, modeling and molecular dynamics, we investigated how the four different types are arranged in a complex. We found that there is a matching pattern in the core of the complex that dictates the position of the four fundamental SNARE types in the bundle, resulting in a QabcR complex. In the cell, several different cognate QabcR-SNARE complexes catalyze the different transport steps between the compartments of the endomembrane system. Each of these cognate QabcR complexes is compiled from a repertoire of about 20 SNARE subtypes. Our studies show that exchange within the four types is largely tolerated structurally, although some non-cognate exchanges lead to structural imbalances. This suggests that SNARE complexes have evolved for a catalytic mechanism, a mechanism that leaves little scope for selectivity beyond the QabcR rule.

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SNARE Modulators and SNARE Mimetic Peptides

Cited by 8 publications

References 138 publications

Conformational Space of the Translocation Domain of Botulinum Toxin: Atomistic Modeling and Mesoscopic Description of the Coiled-Coil Helix Bundle

Conformational Space of the Translocation Domain of Botulinum Toxin: Atomistic Modeling and Mesoscopic Description of the Coiled-Coil Helix Bundle

Conformational Space of the Translocation Domain of Botulinum Toxin: Atomistic Modeling and Mesoscopic Description of the Coiled-Coil Helix Bundle

A look beyond the QR code of SNARE proteins

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