Magic angle spinning NMR of viruses

Quinn, Caitlin M.; Lu, Manman; Suiter, Christopher L.; Hou, Guangjin; Zhang, Huilan; Polenova, Tatyana

doi:10.1016/j.pnmrs.2015.02.003

Cited by 23 publications

(20 citation statements)

References 258 publications

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“…Furthermore, while biochemical and structural studies have provided insight into TRIM5α-capsid interactions (23,26,34,35), atomic-level characterization has not been possible to date. Magic-angle spinning (MAS) nuclear magnetic resonance (NMR) is uniquely suited to elucidate the molecular details of the TRIM5α-capsid interactions and has proven to be a powerful technique for studying HIV-1 protein assemblies (36). Here we report direct, residuespecific evidence of intermolecular interactions between TRIM5α CC-SPRY (coiled-coil and SPRY domains; Fig.…”

Section: Significancementioning

confidence: 92%

Dynamic regulation of HIV-1 capsid interaction with the restriction factor TRIM5α identified by magic-angle spinning NMR and molecular dynamics simulations

Quinn

Wang

Fritz

et al. 2018

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

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The host factor protein TRIM5α plays an important role in restricting the host range of HIV-1, interfering with the integrity of the HIV-1 capsid. TRIM5 triggers an antiviral innate immune response by functioning as a capsid pattern recognition receptor, although the precise mechanism by which the restriction is imposed is not completely understood. Here we used an integrated magic-angle spinning nuclear magnetic resonance and molecular dynamics simulations approach to characterize, at atomic resolution, the dynamics of the capsid’s hexameric and pentameric building blocks, and the interactions with TRIM5α in the assembled capsid. Our data indicate that assemblies in the presence of the pentameric subunits are more rigid on the microsecond to millisecond timescales than tubes containing only hexamers. This feature may be of key importance for controlling the capsid’s morphology and stability. In addition, we found that TRIM5α binding to capsid induces global rigidification and perturbs key intermolecular interfaces essential for higher-order capsid assembly, with structural and dynamic changes occurring throughout the entire CA polypeptide chain in the assembly, rather than being limited to a specific protein-protein interface. Taken together, our results suggest that TRIM5α uses several mechanisms to destabilize the capsid lattice, ultimately inducing its disassembly. Our findings add to a growing body of work indicating that dynamic allostery plays a pivotal role in capsid assembly and HIV-1 infectivity.

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Section: Significancementioning

confidence: 92%

Dynamic regulation of HIV-1 capsid interaction with the restriction factor TRIM5α identified by magic-angle spinning NMR and molecular dynamics simulations

Quinn

Wang

Fritz

et al. 2018

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

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“…Virus capsids can also be studied by solid‐state NMR . NMR chemical shifts, and especially those of carbon‐13, are highly sensitive to backbone dihedral angles, and can detect conformational differences by chemical‐shift perturbations, typically when an interactant is added, or in protein complexes (for a review see Ref.…”

Section: Figurementioning

confidence: 99%

Localizing Conformational Hinges by NMR: Where Do Hepatitis B Virus Core Proteins Adapt for Capsid Assembly?

et al. 2018

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The hepatitis B virus (HBV) icosahedral nucleocapsid is assembled from 240 chemically identical core protein molecules and, structurally, comprises four groups of symmetrically nonequivalent subunits. We show here that this asymmetry is reflected in solid-state NMR spectra of the capsids, in which peak splitting is observed for a subset of residues. We compare this information to dihedral angle variations from available 3D structures and also to computational predictions of "dynamic" domains and molecular hinges. We find that although, at the given resolution, dihedral angles variations directly obtained from the X-ray structures are not precise enough to be interpreted, the chemical-shift information from NMR correlates, and interestingly goes beyond, information from bioinformatics approaches. Our study reveals the high sensitivity with which NMR can detect the residues allowing the subtle conformational adaptations needed in lattice formation. Our findings are important for understanding the formation and modulation of protein assemblies in general.

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“…Biological solid-state NMR (ssNMR) has undergone tremendous development in recent years, providing new insights into the structure and dynamics of membrane proteins, protein aggregates, and a variety of other biologically interesting samples (Goldbourt 2013; Knight et al 2013; Loquet et al 2013; Porcelli et al 2013; Weingarth and Baldus 2013; Wang and Ladizhansky 2014; Andreas et al 2015; Quinn et al 2015; Ravera et al 2015). Most of these results stem from the use of magic angle spinning (MAS) ssNMR.…”

Section: Introductionmentioning

confidence: 99%

On the use of ultracentrifugal devices for routine sample preparation in biomolecular magic-angle-spinning NMR

et al. 2017

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A number of recent advances in the field of magic-angle-spinning (MAS) solid-state NMR have enabled its application to a range of biological systems of ever increasing complexity. To retain biological relevance, these samples are increasingly studied in a hydrated state. At the same time, experimental feasibility requires the sample preparation process to attain a high sample concentration within the final MAS rotor. We discuss these considerations, and how they have led to a number of different approaches to MAS NMR sample preparation. We describe our experience of how custom-made (or commercially available) ultracentrifugal devices can facilitate a simple, fast and reliable sample preparation process. A number of groups have since adopted such tools, in some cases to prepare samples for sedimentation-style MAS NMR experiments. Here we argue for a more widespread adoption of their use for routine MAS NMR sample preparation.

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Magic angle spinning NMR of viruses

Cited by 23 publications

References 258 publications

Dynamic regulation of HIV-1 capsid interaction with the restriction factor TRIM5α identified by magic-angle spinning NMR and molecular dynamics simulations

Dynamic regulation of HIV-1 capsid interaction with the restriction factor TRIM5α identified by magic-angle spinning NMR and molecular dynamics simulations

Localizing Conformational Hinges by NMR: Where Do Hepatitis B Virus Core Proteins Adapt for Capsid Assembly?

On the use of ultracentrifugal devices for routine sample preparation in biomolecular magic-angle-spinning NMR

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