scholarly journals SARS-CoV-2 Virion Stabilization by Zn Binding

2020 ◽  
Author(s):  
Silvia Morante ◽  
Giovanni La Penna ◽  
Giancarlo C. Rossi ◽  
Francesco Stellato
Keyword(s):  
Host Cell ◽  
Structural Study ◽  
Crucial Role ◽  
Disulfide Bonds ◽  
Zinc Binding ◽  
Proof Of Concept ◽  
Slowing Down ◽  
Viral Maturation ◽  
Cellular Zinc

Zinc plays a crucial role in the process of virion maturation inside the host cell. The accessory Cys-rich proteins expressed in SARS-CoV-2 by genes ORF7a and ORF8 are likely involved in zinc binding and in interactions with cellular antigens activated by extensive disulfide bonds. In this report we provide a proof of concept for the feasibility of a structural study of orf7a and orf8 proteins. A conceivable hypothesis is that lack of cellular zinc, or substitution thereof, might lead to a significant slowing down of viral maturation.

scholarly journals SARS-CoV-2 Virion Stabilization by Zn Binding

2020 ◽  
Author(s):  
Silvia Morante ◽  
Giovanni La Penna ◽  
Giancarlo C. Rossi ◽  
Francesco Stellato
Keyword(s):  
Host Cell ◽  
Structural Study ◽  
Crucial Role ◽  
Disulfide Bonds ◽  
Zinc Binding ◽  
Proof Of Concept ◽  
Slowing Down ◽  
Viral Maturation ◽  
Cellular Zinc

Zinc plays a crucial role in the process of virion maturation inside the host cell. The accessory Cys-rich proteins expressed in SARS-CoV-2 by genes ORF7a and ORF8 are likely involved in zinc binding and in interactions with cellular antigens activated by extensive disulfide bonds. In this report we provide a proof of concept for the feasibility of a structural study of orf7a and orf8 proteins. We make the point that lack of cellular zinc, or substitution thereof, might lead to a significant slowing down of viral maturation.

scholarly journals The methyltransferase METTL9 mediates pervasive 1-methylhistidine modification in mammalian proteomes

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Erna Davydova ◽  
Tadahiro Shimazu ◽  
Maren Kirstin Schuhmacher ◽  
Magnus E. Jakobsson ◽  
Hanneke L. D. M. Willemen ◽  
...  
Keyword(s):  
Amino Acid ◽  
Protein Function ◽  
Crucial Role ◽  
Complex I ◽  
Protein Modification ◽  
Zinc Binding ◽  
Functional Studies ◽  
Mitochondrial Respiratory Complex ◽  
Respiratory Complex I ◽  
Broad Specificity

AbstractPost-translational methylation plays a crucial role in regulating and optimizing protein function. Protein histidine methylation, occurring as the two isomers 1- and 3-methylhistidine (1MH and 3MH), was first reported five decades ago, but remains largely unexplored. Here we report that METTL9 is a broad-specificity methyltransferase that mediates the formation of the majority of 1MH present in mouse and human proteomes. METTL9-catalyzed methylation requires a His-x-His (HxH) motif, where “x” is preferably a small amino acid, allowing METTL9 to methylate a number of HxH-containing proteins, including the immunomodulatory protein S100A9 and the NDUFB3 subunit of mitochondrial respiratory Complex I. Notably, METTL9-mediated methylation enhances respiration via Complex I, and the presence of 1MH in an HxH-containing peptide reduced its zinc binding affinity. Our results establish METTL9-mediated 1MH as a pervasive protein modification, thus setting the stage for further functional studies on protein histidine methylation.

scholarly journals Progression from remodeling to hibernation of ribosomes in zinc-starved mycobacteria

2020 ◽  
Vol 117 (32) ◽  
pp. 19528-19537
Author(s):  
Yunlong Li ◽  
Jamie H. Corro ◽  
Christopher D. Palmer ◽  
Anil K. Ojha
Keyword(s):  
Zinc Concentration ◽  
Specific Protein ◽  
Zinc Binding ◽  
Free Form ◽  
Dependent Manner ◽  
Drug Resistant ◽  
Zinc Depletion ◽  
Cellular Zinc ◽  
Mouse Lungs ◽  
Insight Into

Zinc starvation in mycobacteria leads to remodeling of ribosomes, in which multiple ribosomal (r-) proteins containing the zinc-binding CXXC motif are replaced by their motif-free paralogues, collectively called C− r-proteins. We previously reported that the 70S C− ribosome is exclusively targeted for hibernation by mycobacterial-specific protein Y (Mpy), which binds to the decoding center and stabilizes the ribosome in an inactive and drug-resistant state. In this study, we delineate the conditions for ribosome remodeling and hibernation and provide further insight into how zinc depletion induces Mpy recruitment to C− ribosomes. Specifically, we show that ribosome hibernation in a batch culture is induced at an approximately two-fold lower cellular zinc concentration than remodeling. We further identify a growth phase in which the C− ribosome remains active, while its hibernation is inhibited by the caseinolytic protease (Clp) system in a zinc-dependent manner. The Clp protease system destabilizes a zinc-bound form of Mpy recruitment factor (Mrf), which is stabilized upon further depletion of zinc, presumably in a zinc-free form. Stabilized Mrf binds to the 30S subunit and recruits Mpy to the ribosome. Replenishment of zinc to cells harboring hibernating ribosomes restores Mrf instability and dissociates Mpy from the ribosome. Finally, we demonstrate zinc-responsive binding of Mpy to ribosomes inMycobacterium tuberculosis(Mtb) and show Mpy-dependent antibiotic tolerance of Mtb in mouse lungs. Together, we propose that ribosome hibernation is a specific and conserved response to zinc depletion in both environmental and pathogenic mycobacteria.

scholarly journals Creep dynamics of athermal amorphous materials: a mesoscopic approach

Soft Matter ◽  
2018 ◽  
Vol 14 (41) ◽  
pp. 8306-8316 ◽  
Author(s):  
Chen Liu ◽  
Ezequiel E. Ferrero ◽  
Kirsten Martens ◽  
Jean-Louis Barrat
Keyword(s):  
Strain Rate ◽  
Yield Stress ◽  
Crucial Role ◽  
Amorphous Materials ◽  
Initial Condition ◽  
Spatial Correlations ◽  
Linear Dynamics ◽  
Slowing Down ◽  
Rate Acceleration ◽  
Experimental Strain

Mesoscale elasto-plastic models are shown to capture the non-linear dynamics of yield stress fluids, reproducing the typical experimental strain rate responses to different applied steps in stress. Moreover, they help us to understand basic processes (e.g. spatial correlations) involved in the strain rate slowing down (creep) and the strain rate acceleration (fluidization) phases, and the crucial role played by the initial condition.

Insulin fibrillation control by specific zinc binding sites

2021 ◽  
Author(s):  
Shira Ben-Shushan ◽  
Yifat Miller
Keyword(s):  
Blood Sugar ◽  
Binding Sites ◽  
Crucial Role ◽  
The Body ◽  
Zinc Binding ◽  
Β Cells ◽  
Sugar Levels

Insulin is naturally released from the β-cells in the pancreas and plays a crucial role in controlling the blood sugar levels in the body. However, it was found that when...

scholarly journals Mason-Pfizer Monkey Virus Envelope Glycoprotein Cycling and Its Vesicular Co-Transport with Immature Particles

Viruses ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 575 ◽  
Author(s):  
Petra Prokšová ◽  
Jan Lipov ◽  
Jaroslav Zelenka ◽  
Eric Hunter ◽  
Hana Langerová ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Life Cycle ◽  
Host Cell ◽  
Envelope Glycoprotein ◽  
Crucial Role ◽  
Intracellular Trafficking ◽  
Virus Envelope ◽  
Trans Golgi Network ◽  
Golgi Network ◽  
Putative Mechanism

The envelope glycoprotein (Env) plays a crucial role in the retroviral life cycle by mediating primary interactions with the host cell. As described previously and expanded on in this paper, Env mediates the trafficking of immature Mason-Pfizer monkey virus (M-PMV) particles to the plasma membrane (PM). Using a panel of labeled RabGTPases as endosomal markers, we identified Env mostly in Rab7a- and Rab9a-positive endosomes. Based on an analysis of the transport of recombinant fluorescently labeled M-PMV Gag and Env proteins, we propose a putative mechanism of the intracellular trafficking of M-PMV Env and immature particles. According to this model, a portion of Env is targeted from the trans-Golgi network (TGN) to Rab7a-positive endosomes. It is then transported to Rab9a-positive endosomes and back to the TGN. It is at the Rab9a vesicles where the immature particles may anchor to the membranes of the Env-containing vesicles, preventing Env recycling to the TGN. These Gag-associated vesicles are then transported to the plasma membrane.

scholarly journals Toxoplasma Uses GRA16 To Upregulate Host c-Myc

mSphere ◽  
2020 ◽  
Vol 5 (3) ◽  
Author(s):  
Michael W. Panas ◽  
John C. Boothroyd
Keyword(s):  
Host Cell ◽  
Protein Phosphatase ◽  
Crucial Role ◽  
Neospora Caninum ◽  
Parasitophorous Vacuole ◽  
Regulatory Subunit ◽  
Close Relative ◽  
Effector Protein ◽  
Animal Cells ◽  
Content Type

ABSTRACT Manipulation of the host cell is a crucial part of life for many intracellular organisms. We have recently come to appreciate the extent to which the intracellular pathogen Toxoplasma gondii reprograms its host cell, and this is illustrated by the marked upregulation of the central regulator c-Myc, an oncogene that coordinates myriad cellular functions. In an effort to identify an effector protein capable of regulating c-Myc, our laboratory constructed a screen for mutant parasites unable to accomplish this upregulation. Interestingly, this screen identified numerous components of a complex located in/on the parasitophorous vacuole membrane necessary to translocate Toxoplasma proteins out into the host cytosol, but it never identified a specific effector protein. Thus, how the parasite upregulates c-Myc has largely been a mystery. Previously, the Toxoplasma dense granule protein GRA16 has been described to bind to one isoform of PP2A-B, a regulatory subunit that coordinates the activity of the catalytic protein phosphatase PP2A. As other PP2A subunits have been reported to target PP2A protein phosphatase activity to c-Myc, subsequently leading to c-Myc destabilization, we examined whether GRA16 has an impact on host c-Myc accumulation. Expression of Toxoplasma’s GRA16 protein in Neospora caninum, a close relative of Toxoplasma that does not naturally upregulate host c-Myc, conferred the ability on Neospora to do this now. Further support was obtained by deleting the GRA16 gene from Toxoplasma and observing a severely diminished ability of Toxoplasma tachyzoites to upregulate host c-Myc. Thus, GRA16 is an effector protein central to Toxoplasma’s ability to upregulate host c-Myc. IMPORTANCE The proto-oncogene c-Myc plays a crucial role in the growth and division of many animal cells. Previous studies have identified an active upregulation of c-Myc by Toxoplasma tachyzoites, suggesting the existence of one or more exported “effector” proteins. The identity of such an effector, however, has not previously been known. Here, we show that a previously known secreted protein, GRA16, plays a crucial role in c-Myc upregulation. This finding will enable further dissection of the precise mechanism and role of c-Myc upregulation in Toxoplasma-infected cells.

OR09-1 The role of zinc binding and the cellular zinc content in regulated growth hormone secretion

2012 ◽  
Vol 22 ◽  
pp. S23
Author(s):  
V. Petkovic ◽  
M.C. Mileta ◽  
A. Eblé ◽  
D.I. Iliev ◽  
G. Binder ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Zinc Content ◽  
Zinc Binding ◽  
Cellular Zinc

Host cell penetration in kinetoplastida and coccidia: a fine structural study

1998 ◽  
Vol 47 ◽  
pp. 149
Author(s):  
H Mehlhorn ◽  
S Langer ◽  
S Walter
Keyword(s):  
Host Cell ◽  
Structural Study ◽  
Cell Penetration

scholarly journals Zinc binding ligands and cellular zinc trafficking: Apo-metallothionein, glutathione, TPEN, proteomic zinc, and Zn-Sp1

2008 ◽  
Vol 102 (3) ◽  
pp. 489-499 ◽  
Author(s):  
Ujala Rana ◽  
Rajendra Kothinti ◽  
Jeffrey Meeusen ◽  
Niloofar M. Tabatabai ◽  
Susan Krezoski ◽  
...  
Keyword(s):  
Zinc Binding ◽  
Cellular Zinc
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