Molecular mechanisms of stress-induced reactivation in mumps virus condensates

Zhang, Xiaojie; Sridharan, S.; Zagoriy, Ievgeniia; Oegema, Christina Eugster; Ching, Cyan; Pflaesterer, Tim; Fung, Herman K.H.; Becher, Isabelle; Poser, Ina; Müller, Christoph; Hyman, Anthony; Savitski, Mikhail M.; Mahamid, Julia

doi:10.1016/j.cell.2023.03.015

Cited by 26 publications

(13 citation statements)

References 112 publications

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“…Also, mild oxidative stress that is short or long can change how proteins in viral condensates interact and make the transition from slow viral replication during latent infections to faster viral replication that increases transcription and virion release by two-to fourfold. 183 Therefore, viruses likely need to control the formation and function of SGs, which are clusters of proteins and RNAs in cells, to ensure successful viral replication that relies on the host translation system. Thus, many single-stranded RNA viruses such as the dengue virus, 184 Japanese encephalitis virus, 185 measles virus, 186 West Nile virus, 184,187 Usutu virus, 188 and Zika virus, 189 all have evolved successful ways to alter and interfere with host SG induction and formation.…”

Section: Sgs and Viral Infections: A Battle For Cellular Controlmentioning

confidence: 99%

Intrinsic factors behind long COVID: IV. Hypothetical roles of the SARS‐CoV‐2 nucleocapsid protein and its liquid–liquid phase separation

Eltayeb,

Al‐Sarraj,

Alharbi

et al. 2024

J of Cellular Biochemistry

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When the SARS‐CoV‐2 virus infects humans, it leads to a condition called COVID‐19 that has a wide spectrum of clinical manifestations, from no symptoms to acute respiratory distress syndrome. The virus initiates damage by attaching to the ACE‐2 protein on the surface of endothelial cells that line the blood vessels and using these cells as hosts for replication. Reactive oxygen species levels are increased during viral replication, which leads to oxidative stress. About three‐fifths (~60%) of the people who get infected with the virus eradicate it from their body after 28 days and recover their normal activity. However, a large fraction (~40%) of the people who are infected with the virus suffer from various symptoms (anosmia and/or ageusia, fatigue, cough, myalgia, cognitive impairment, insomnia, dyspnea, and tachycardia) beyond 12 weeks and are diagnosed with a syndrome called long COVID. Long‐term clinical studies in a group of people who contracted SARS‐CoV‐2 have been contrasted with a noninfected matched group of people. A subset of infected people can be distinguished by a set of cytokine markers to have persistent, low‐grade inflammation and often self‐report two or more bothersome symptoms. No medication can alleviate their symptoms efficiently. Coronavirus nucleocapsid proteins have been investigated extensively as potential drug targets due to their key roles in virus replication, among which is their ability to bind their respective genomic RNAs for incorporation into emerging virions. This review highlights basic studies of the nucleocapsid protein and its ability to undergo liquid–liquid phase separation. We hypothesize that this ability of the nucleocapsid protein for phase separation may contribute to long COVID. This hypothesis unlocks new investigation angles and could potentially open novel avenues for a better understanding of long COVID and treating this condition.

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Section: Sgs and Viral Infections: A Battle For Cellular Controlmentioning

confidence: 99%

Intrinsic factors behind long COVID: IV. Hypothetical roles of the SARS‐CoV‐2 nucleocapsid protein and its liquid–liquid phase separation

Eltayeb,

Al‐Sarraj,

Alharbi

et al. 2024

J of Cellular Biochemistry

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“…We have also used this protocol with slight modifications for determining the structure of nucleocapsids inside cells after 6 hours of potassium arsenate or sodium arsenite treatment. 1…”

Section: Before You Beginmentioning

confidence: 99%

“…The 13,000 g pellet enriched with nucleocapsids was subjected to heparin treatment in order to induce straightening of the nucleaocapsids. 1 Straight nucleocapsids proved beneficial for obtaining high resolution maps.…”

Section: Before You Beginmentioning

confidence: 99%

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Subtomogram averaging of helical filaments in cryo-electron tomography

Zhang,

Mahamid

2024

Preprint

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Helical filaments are essential macromolecular elements in cellular organization and dynamics. Recent advances in cryo-electron tomography allow faithful imaging of isolated or in-cell helical filaments. Here, we present a protocol to generate density maps at sub-nanometer resolution of helical filaments by subtomogram averaging, exemplified with isolated mumps virus nucleocapsids and their in-cell form as an extension of the method. We detail procedures from pre-processing of tilt series frames to refinement of reconstructed averages for streamlined data processing of helical filaments.

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“…Over the past few decades, numerous efforts have been made on the development of methods for directly visualizing proteins in living cells, including nuclear magnetic resonance (NMR) spectroscopy, in vivo chemical cross-linking mass spectrometry (XL-MS), cryo-electron tomography (cryo-ET), light microscopy, and various computational approaches, enabling researchers to derive insights into intracellular protein structures, protein folding, protein dynamics, and protein interactions in their native environment. Cryo-ET can visualize the 3D structures of macromolecules, viruses, and cellular components, as well as directly study protein–protein interactions, the assembly and operation of protein machinery, and the phase separation of biomacromolecules in near-nanometer resolution . Besides, the development of fluorescent proteins and advanced imaging techniques has significantly expanded the capabilities of light microscopy for studying protein structure within cells .…”

Section: Introductionmentioning

confidence: 99%

Progress, Challenges and Opportunities of NMR and XL-MS for Cellular Structural Biology

Zhang,

Zhao,

Gong

et al. 2024

JACS Au

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The validity of protein structures and interactions, whether determined under ideal laboratory conditions or predicted by AI tools such as Alphafold2, to precisely reflect those found in living cells remains to be examined. Moreover, understanding the changes in protein structures and interactions in response to stimuli within living cells, under both normal and disease conditions, is key to grasping proteins' functionality and cellular processes. Nevertheless, achieving high-resolution identification of these protein structures and interactions within living cells presents a technical challenge. In this Perspective, we summarize the recent advancements in in-cell nuclear magnetic resonance (NMR) and in vivo cross-linking mass spectrometry (XL-MS) for studying protein structures and interactions within a cellular context. Additionally, we discuss the challenges, opportunities, and potential benefits of integrating in-cell NMR and in vivo XL-MS in future research to offer an exhaustive approach to studying proteins in their natural habitat.

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Molecular mechanisms of stress-induced reactivation in mumps virus condensates

Cited by 26 publications

References 112 publications

Intrinsic factors behind long COVID: IV. Hypothetical roles of the SARS‐CoV‐2 nucleocapsid protein and its liquid–liquid phase separation

Intrinsic factors behind long COVID: IV. Hypothetical roles of the SARS‐CoV‐2 nucleocapsid protein and its liquid–liquid phase separation

Subtomogram averaging of helical filaments in cryo-electron tomography

Progress, Challenges and Opportunities of NMR and XL-MS for Cellular Structural Biology

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