Immature HIV-1 lattice assembly dynamics are regulated by scaffolding from nucleic acid and the plasma membrane

Pak, Alexander J.; Grime, John M. A.; Sengupta, Prabuddha; Chen, Antony K.; Durumeric, Aleksander E. P.; Srivastava, Anand; Yeager, Mark; Briggs, John; Lippincott‐Schwartz, Jennifer; Voth, Gregory A.

doi:10.1073/pnas.1706600114

Cited by 93 publications

(109 citation statements)

References 104 publications

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“…In this work we systematically investigate the role of M2 in budding at a coarse-grained (CG) resolution using a combination of computer simulations and experiments. The use of theory and simulation to study fundamental processes has gained widespread popularity in the biophysical sciences, with CG models successfully applied to the investigation of processes related to viral budding such as vesicle budding by antimicrobial peptides (12), viral proteins and capsids (13)(14)(15)(16), dynamin constriction (17), and nanoparticle endocytosis (18)(19)(20)(21). In our simulations, theoretical as well as experimental constraints are taken into account to ensure that the system studied presents a close correspondence with biological reality.…”

mentioning

confidence: 99%

Entropic forces drive clustering and spatial localization of influenza A M2 during viral budding

Madsen

Grime

Rossman

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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The influenza A matrix 2 (M2) transmembrane protein facilitates virion release from the infected host cell. In particular, M2 plays a role in the induction of membrane curvature and/or in the scission process whereby the envelope is cut upon virion release. Here we show using coarse-grained computer simulations that various M2 assembly geometries emerge due to an entropic driving force, resulting in compact clusters or linearly extended aggregates as a direct consequence of the lateral membrane stresses. Conditions under which these protein assemblies will cause the lipid membrane to curve are explored, and we predict that a critical cluster size is required for this to happen. We go on to demonstrate that under the stress conditions taking place in the cellular membrane as it undergoes large-scale membrane remodeling, the M2 protein will, in principle, be able to both contribute to curvature induction and sense curvature to line up in manifolds where local membrane line tension is high. M2 is found to exhibit linactant behavior in liquid-disordered-liquid-ordered phase-separated lipid mixtures and to be excluded from the liquid-ordered phase, in near-quantitative agreement with experimental observations. Our findings support a role for M2 in membrane remodeling during influenza viral budding both as an inducer and a sensor of membrane curvature, and they suggest a mechanism by which localization of M2 can occur as the virion assembles and releases from the host cell, independent of how the membrane curvature is produced.

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mentioning

confidence: 99%

Entropic forces drive clustering and spatial localization of influenza A M2 during viral budding

Madsen

Grime

Rossman

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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“…They have studied the basic principles of capsid assembly and the effect of varied conditions such as molecular crowding, concentration of capsid assembly and the conformational changes associated with it. In another study by Pak, a coarse-grained simulation of sub-nanometer resolution has been applied to study the interaction network of HIV-1 assembly and budding of Gag polyprotein [142]. They have suggested the putative role of the Gag protein, RNA and cell membranes in the initial stages of immature HIV-1 lattice assembly.…”

Section: Coarse-grained Models and Biomolecular Complexesmentioning

confidence: 99%

Recent Advances in Coarse-Grained Models for Biomolecules and Their Applications

Singh

2019

IJMS

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Molecular dynamics simulations have emerged as a powerful tool to study biological systems at varied length and timescales. The conventional all-atom molecular dynamics simulations are being used by the wider scientific community in routine to capture the conformational dynamics and local motions. In addition, recent developments in coarse-grained models have opened the way to study the macromolecular complexes for time scales up to milliseconds. In this review, we have discussed the principle, applicability and recent development in coarse-grained models for biological systems. The potential of coarse-grained simulation has been reviewed through state-of-the-art examples of protein folding and structure prediction, self-assembly of complexes, membrane systems and carbohydrates fiber models. The multiscale simulation approaches have also been discussed in the context of their emerging role in unravelling hierarchical level information of biosystems. We conclude this review with the future scope of coarse-grained simulations as a constantly evolving tool to capture the dynamics of biosystems.

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“…Recently, using coarse grained molecular simulation Pak et al (40) has estimated that the oligomerization via CA-CA…”

Section: R a F Tmentioning

confidence: 99%

Live single molecule microscopy of HIV-1 assembly in host T cells reveals a spatio-temporal effect of the viral genome

Floderer

Masson

Boiley

et al. 2018

Preprint

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Monitoring virus assembly dynamic at the nanoscale level in host cells remains a major challenge. Human Immunodeficiency Virus type 1 (HIV-1) components are addressed to the plasma membrane where they assemble to form spherical particles of 100nm in diameter. HIV-1 Gag protein expression alone is sufficient to produce virus-like particles (VLPs) that resemble immature virus. Here, we monitored Gag assembly in host CD4 T lymphocytes using single molecule dynamics microscopy and energy mapping. A workflow allowing long time recordings of single Gag molecule localization, diffusion and effective energy maps was developed for robust quantitative analysis of HIV assembly and budding. Comparison of numerous cell plasma membrane assembling platforms in cells expressing wild type or assembly-defective Gag proteins showed that VLP formation last 15 minutes, with an assembly time of 5 minutes, and that the nucleocapsid domain is mandatory. Importantly, it reveals that the viral genome coordinates spatio-temporally HIV-1 assembly.

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Immature HIV-1 lattice assembly dynamics are regulated by scaffolding from nucleic acid and the plasma membrane

Cited by 93 publications

References 104 publications

Entropic forces drive clustering and spatial localization of influenza A M2 during viral budding

Entropic forces drive clustering and spatial localization of influenza A M2 during viral budding

Recent Advances in Coarse-Grained Models for Biomolecules and Their Applications

Live single molecule microscopy of HIV-1 assembly in host T cells reveals a spatio-temporal effect of the viral genome

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