Influence of Nuclear Localization Sequences on the Intracellular Fate of Gold Nanoparticles

ACS Nano ◽  
2021 ◽  
Author(s):  
Daniela Drescher ◽  
Tina Büchner ◽  
Petra Schrade ◽  
Heike Traub ◽  
Stephan Werner ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Nuclear Localization ◽  
Nuclear Localization Sequences ◽  
Intracellular Fate

The C-terminal domain of Salmonid Alphavirus nonstructural protein 2 (nsP2) is essential and sufficient to block RIG-I pathway induction and interferon-mediated antiviral response.

2021 ◽  
Author(s):  
Raphaël Jami ◽  
Emilie Mérour ◽  
Julie Bernard ◽  
Annie Lamoureux ◽  
Jean K. Millet ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Innate Immune Response ◽  
Nuclear Localization ◽  
Innate Immune ◽  
Type I ◽  
Annual Growth Rate ◽  
Structural Protein ◽  
Terminal Domain ◽  
Nuclear Localization Sequences

Salmonid alphavirus (SAV) is an atypical alphavirus, which has a considerable impact on salmon and trout farms. Unlike other alphaviruses such as the chikungunya virus, SAV is transmitted without an arthropod vector, and does not cause cell shut-off during infection. The mechanisms by which SAV escapes the host immune system remain unknown. By studying the role of SAV proteins on the RIG-I signaling cascade, the first line of defense of the immune system during infection, we demonstrated that non-structural protein 2 (nsP2) effectively blocks the induction of type I interferon (IFN). This inhibition, independent of the protease activity carried by nsP2, occurs downstream of IRF3 which is the transcription factor allowing the activation of the IFN promoter and its expression. The inhibitory effect of nsP2 on the RIG-I pathway depends on the localization of nsP2 in the host cell nucleus which is linked to two nuclear localization sequences (NLS) located in its C-terminal part. The C-terminal domain of nsP2 by itself is sufficient and necessary to block IFN induction. Mutation of the NLS of nsP2 is deleterious to the virus. Finally, nsP2 does not interact with IRF3, indicating that its action is possible through a targeted interaction within discrete areas of chromatin, as suggested by its punctate distribution observed in the nucleus. These results therefore demonstrate a major role for nsP2 in the control by SAV of the host cell’s innate immune response. Importance The global consumption of fish continues to rise and the future demand cannot be met by capture fisheries alone due to limited stocks of wild fish. Aquaculture is currently the world’s fastest growing food production sector with an annual growth rate of 6-8 %. Recurrent outbreaks of SAV result in significant economic losses with serious environmental consequences on wild stocks. While the clinical and pathological signs of SAV infection are fairly well known, the molecular mechanisms involved are poorly described. In the present study, we focus on the non-structural protein nsP2 and characterize a specific domain containing nuclear localization sequences that are critical for the inhibition of the host innate immune response mediated by the RIG-I pathway.

scholarly journals Nuclear Localization Sequences in Cytomegalovirus Capsid Assembly Proteins (UL80 Proteins) Are Required for Virus Production: Inactivating NLS1, NLS2, or Both Affects Replication to Strikingly Different Extents

2008 ◽  
Vol 82 (11) ◽  
pp. 5381-5389 ◽  
Author(s):  
Nang L. Nguyen ◽  
Amy N. Loveland ◽  
Wade Gibson
Keyword(s):  
Nuclear Localization ◽  
Infectious Virus ◽  
Nuclear Translocation ◽  
Virus Production ◽  
Wild Type Virus ◽  
Capsid Assembly ◽  
Scaffolding Proteins ◽  
Hcmv Replication ◽  
Protease Precursor ◽  
Nuclear Localization Sequences

ABSTRACT Scaffolding proteins of spherical prokaryotic and eukaryotic viruses have critical roles in capsid assembly. The primary scaffolding components of cytomegalovirus, called the assembly protein precursor (pAP, pUL80.5) and the maturational protease precursor (pPR, pUL80a), contain two nuclear localization sequences (NLS1 and NLS2), at least one of which is required in coexpression experiments to translocate the major capsid protein (MCP, pUL85) into the nucleus. In the work reported here, we have mutated NLS1 and NLS2, individually or together, in human cytomegalovirus (HCMV, strain AD169) bacmid-derived viruses to test their effects on virus replication. Consistent with results from earlier transfection/coexpression experiments, both single-mutant bacmids gave rise to infectious virus but the double mutant did not. In comparisons with the wild-type virus, both mutants showed slower cell-to-cell spread; decreased yields of infectious virus (3-fold lower for NLS1− and 140-fold lower for NLS2−); reduced efficiency of pAP, pPR, and MCP nuclear translocation (sixfold lower for NLS1− and eightfold lower for NLS2−); increased amounts of a 120-kDa MCP fragment; and reduced numbers of intranuclear capsids. All effects were more severe for the NLS2− mutant than the NLS1− mutant, and a distinguishing feature of cells infected with the NLS2− mutant was the accumulation of large, UL80 protein-containing structures within the nucleus. We conclude that these NLS assist in the nuclear translocation of MCP during HCMV replication and that NLS2, which is unique to the betaherpesvirus UL80 homologs, may have additional involvements during replication.

scholarly journals REST/NRSF-Interacting LIM Domain Protein, a Putative Nuclear Translocation Receptor

2003 ◽  
Vol 23 (24) ◽  
pp. 9025-9031 ◽  
Author(s):  
Masahito Shimojo ◽  
Louis B. Hersh
Keyword(s):  
Nuclear Localization ◽  
Nuclear Translocation ◽  
Protein A ◽  
Lim Domain ◽  
Nuclear Targeting ◽  
Lim Domains ◽  
Lim Domain Protein ◽  
Domain Protein ◽  
Nuclear Localization Sequences ◽  
Novel Protein

ABSTRACT The transcriptional repressor REST/NRSF (RE-1 silencing transcription factor/neuron-restrictive silencer factor) and the transcriptional regulator REST4 share an N-terminal zinc finger domain structure involved in nuclear targeting. Using this domain as bait in a yeast two-hybrid screen, a novel protein that contains three LIM domains, putative nuclear localization sequences, protein kinase A phosphorylation sites, and a CAAX prenylation motif was isolated. This protein, which is localized around the nucleus, is involved in determining the nuclear localization of REST4 and REST/NRSF. We propose the name RILP, for REST/NRSF-interacting LIM domain protein, to label this novel protein. RILP appears to serve as a nuclear receptor for REST/NRSF, REST4, and possibly other transcription factors.

The yeast nucleoporin Nsp1 binds nuclear localization sequences in vitro

1996 ◽  
Vol 74 (3) ◽  
pp. 363-372 ◽  
Author(s):  
Werner Barth ◽  
Ursula Stochaj
Keyword(s):  
Nuclear Localization ◽  
Specific Binding ◽  
T Antigen ◽  
Nuclear Localization Sequence ◽  
Nuclear Pore ◽  
Sv40 T Antigen ◽  
Nuclear Targeting ◽  
Nuclear Localization Sequences

Facilitated transport of proteins into the nucleus requires nuclear localization sequences (NLSs) be present in the protein destined for the nucleus. The specific binding of NLSs by components of the nuclear transport apparatus is essential for these targeting reactions. We now report that the yeast nucleoporin Nsp1 binds specifically nuclear localization sequences in vitro. This nucleoporin recognizes several NLSs that are functional for nuclear targeting in vivo, including the NLS of SV40 T-antigen and of the yeast transcription factor Gal4. Nsp1 is organized into three domains, and we have located NLS binding sites to the N-terminal portion and the middle repetitive region of the protein. For the interaction between the NLS of SV40 T-antigen and Nsp1, we obtained association constants of 1.2 × 107 M−1 and 5 × 107 M−1. An association constant of 5 × 107 M−1 was determined for NLS binding to the repetitive domain of Nsp1. We analyzed binding of Nsp1 and its domains to a mutant version of the NLS derived from SV40 T-antigen, which poorly functions for nuclear targeting in vivo. The affinity for the mutant signal was about two orders of magnitude lower than for the wild-type NLS.Key words: Nsp1, nuclear pore complex, nucleoporin, nuclear localization sequence, protein targeting, yeast.

Cyclin H is targeted to the nucleus by C-terminal nuclear localization sequences

2005 ◽  
Vol 62 (12) ◽  
pp. 1379-1387 ◽  
Author(s):  
A. Krempler ◽  
S. Kartarius ◽  
J. Günther ◽  
M. Montenarh
Keyword(s):  
Nuclear Localization ◽  
Nuclear Localization Sequences
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