Switching between Successful and Dead-End Intermediates in Membrane Fusion

Molotkovsky, R. J.; Galimzyanov, Timur R.; Jiménez-Munguía, Irene; Павлов, Константин; Batishchev, Oleg V.; Akimov, Sergey A.

doi:10.3390/ijms18122598

Cited by 18 publications

(26 citation statements)

References 67 publications

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“…This fusion mechanism was experimentally demonstrated for a number of systems, including purely lipidic [ 16 , 18 , 19 , 20 ] and lipid-protein [ 21 , 22 , 23 , 24 , 25 ] systems. Although there are other possible ways of evolution of the system of fusing membranes, sometimes occurring with the rupture of one of the interacting membranes at the intermediate stage [ 26 , 27 ], it is the trajectory associated with radial expansion of intermediate stalk that proved to be highly efficient, whereas others do not result in complete fusion, i.e., they lead to a dead end [ 27 ]. In this respect, it is the lipid component of the biological membranes that plays an important role in fusion.…”

Section: Introductionmentioning

confidence: 99%

Phosphatidylcholine Membrane Fusion Is pH-Dependent

Akimov

Polynkin

Jiménez-Munguía

et al. 2018

IJMS

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Membrane fusion mediates multiple vital processes in cell life. Specialized proteins mediate the fusion process, and a substantial part of their energy is used for topological rearrangement of the membrane lipid matrix. Therefore, the elastic parameters of lipid bilayers are of crucial importance for fusion processes and for determination of the energy barriers that have to be crossed for the process to take place. In the case of fusion of enveloped viruses (e.g., influenza) with endosomal membrane, the interacting membranes are in an acidic environment, which can affect the membrane’s mechanical properties. This factor is often neglected in the analysis of virus-induced membrane fusion. In the present work, we demonstrate that even for membranes composed of zwitterionic lipids, changes of the environmental pH in the physiologically relevant range of 4.0 to 7.5 can affect the rate of the membrane fusion notably. Using a continual model, we demonstrated that the key factor defining the height of the energy barrier is the spontaneous curvature of the lipid monolayer. Changes of this parameter are likely to be caused by rearrangements of the polar part of lipid molecules in response to changes of the pH of the aqueous solution bathing the membrane.

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Section: Introductionmentioning

confidence: 99%

Phosphatidylcholine Membrane Fusion Is pH-Dependent

Akimov

Polynkin

Jiménez-Munguía

et al. 2018

IJMS

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“…The equilibrium distance H 0 between the membranes is determined by the balance of hydration repulsion forces and the attraction induced by fusion peptides, and it can vary depending on the number of proteins in the fusion rosette and on the curvature of the membranes undergoing fusion. According to various estimates [ 17 , 20 , 51 ], this value is of the order of several nanometers. According to Figure 5 , small H 0 values correspond to the situation when rafts are not favorable for fusion, while the large values—to the situation when rafts facilitate it.…”

Section: Discussionmentioning

confidence: 99%

“…In this paper, we theoretically show that in the case of HIV, insertion of viral fusion peptide into the region of the raft boundary promotes viral fusion. In our work, we use a mechanistic approach for the membrane description successfully used for theoretical investigation of various membrane systems [ 8 , 9 , 11 , 16 , 17 ]. In the framework of this approach, the insertion of any peptide into the membrane is described by the averaged geometric characteristics: depth and width of the insertion.…”

Section: Discussionmentioning

confidence: 99%

“…Earlier, we have demonstrated that there is a strong correlation between the depth of the viral fusion peptide incorporation into a monolayer of the target cell membrane (which is equivalent to generation of the membrane curvature) and the height of the energy barrier for virus-induced membrane fusion [ 16 , 17 ]. According to the generally adopted theory, membrane fusion occurs in several stages [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

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Lateral Membrane Heterogeneity Regulates Viral-Induced Membrane Fusion during HIV Entry

Molotkovsky

Alexandrova

Galimzyanov

et al. 2018

IJMS

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Sphingomyelin- and cholesterol- enriched membrane domains, commonly referred to as “rafts” play a crucial role in a large number of intra- and intercellular processes. Recent experiments suggest that not only the volumetric inhomogeneity of lipid distribution in rafts, but also the arrangement of the 1D boundary between the raft and the surrounding membrane is important for the membrane-associated processes. The reason is that the boundary preferentially recruits different peptides, such as HIV (human immunodeficiency virus) fusion peptide. In the present work, we report a theoretical investigation of mechanisms of influence of the raft boundary arrangement upon virus-induced membrane fusion. We theoretically predict that the raft boundary can act as an attractor for viral fusion peptides, which preferentially distribute into the vicinity of the boundary, playing the role of ‘line active components’ of the membrane (‘linactants’). We have calculated the height of the fusion energy barrier and demonstrated that, in the case of fusion between HIV membrane and the target cell, presence of the raft boundary in the vicinity of the fusion site facilitates fusion. The results we obtained can be further generalized to be applicable to other enveloped viruses.

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“…All expressions were obtained analytically, but we do not provide them because of their extreme bulkiness. The methodology for finding elastic energy is described in more detail in [69,70,71].…”

Section: Figure A1mentioning

confidence: 99%

The Effect of Transmembrane Protein Shape on Surrounding Lipid Domain Formation by Wetting

et al. 2019

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Signal transduction through cellular membranes requires the highly specific and coordinated work of specialized proteins. Proper functioning of these proteins is provided by an interplay between them and the lipid environment. Liquid-ordered lipid domains are believed to be important players here, however, it is still unclear whether conditions for a phase separation required for lipid domain formation exist in cellular membranes. Moreover, membrane leaflets are compositionally asymmetric, that could be an obstacle for the formation of symmetric domains spanning the lipid bilayer. We theoretically show that the presence of protein in the membrane leads to the formation of a stable liquid-ordered lipid phase around it by the mechanism of protein wetting by lipids, even in the absence of conditions necessary for the global phase separation in the membrane. Moreover, we show that protein shape plays a crucial role in this process, and protein conformational rearrangement can lead to changes in the size and characteristics of surrounding lipid domains.

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Switching between Successful and Dead-End Intermediates in Membrane Fusion

Cited by 18 publications

References 67 publications

Phosphatidylcholine Membrane Fusion Is pH-Dependent

Phosphatidylcholine Membrane Fusion Is pH-Dependent

Lateral Membrane Heterogeneity Regulates Viral-Induced Membrane Fusion during HIV Entry

The Effect of Transmembrane Protein Shape on Surrounding Lipid Domain Formation by Wetting

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