scholarly journals Inhibition of Enveloped RNA Virus Formation by Peptides Corresponding to Glycoprotein Sequences

1992 ◽  
Vol 3 (1) ◽  
pp. 31-36 ◽  
Author(s):  
N. C. Collier ◽  
S. P. Adams ◽  
H. Weingarten ◽  
M. J. Schlesinger
Keyword(s):  
Protein Interactions ◽  
Sindbis Virus ◽  
Therapeutic Potential ◽  
Virus Assembly ◽  
Rna Virus ◽  
Amino Acid Sequences ◽  
Proteolytic Processing ◽  
Protein Protein Interactions ◽  
Inhibitory Peptide ◽  
Vesicular Stomatitis

Peptides, corresponding to amino acid sequences in the cytoplasmic domains of the transmembranal glycoproteins encoded by Sindbis and vesicular stomatitis viruses, inhibited release of virus particles and infectious virus when added to infected cells for a 2h period during a one-cycle growth curve. Each inhibitory peptide was specific for its intended virus. The shortest peptide with antiviral activity for Sindbis virus contained six amino acids, and a related peptide that was acylated at the amino terminus with octanoic acid was ten-fold more potent as an inhibitor. Neither of these peptides affected the synthesis of viral structural proteins, but a third peptide inhibited proteolytic processing of the Sindbis virus E2 glycoprotein. Inhibition of vesicular stomatitis virus particle release was dose-dependent in the range of 50–400 μg ml−1 for a peptide corresponding to the G glycoprotein cytoplasmic domain. We postulate that these peptides competitively inhibit attachment of the glycoprotein to intracellular virus structures during assembly of the virion. Thus, drugs, based on peptides that mimic the protein-protein interactions required for virus assembly, may have therapeutic potential.

scholarly journals Bcl-2 and FKBP12 bind to IP3 and ryanodine receptors at overlapping sites: the complexity of protein–protein interactions for channel regulation

2015 ◽  
Vol 43 (3) ◽  
pp. 396-404 ◽  
Author(s):  
Tim Vervliet ◽  
Jan B. Parys ◽  
Geert Bultynck
Keyword(s):  
Protein Interactions ◽  
Hippocampal Neurons ◽  
Binding Protein ◽  
Ryanodine Receptors ◽  
B Cell Lymphoma ◽  
Experimental Models ◽  
Amino Acid Sequences ◽  
Protein Protein Interactions ◽  
Fk506 Binding Protein ◽  
Fk506 Binding Proteins

The 12- and 12.6-kDa FK506-binding proteins, FKBP12 (12-kDa FK506-binding protein) and FKBP12.6 (12.6-kDa FK506-binding protein), have been implicated in the binding to and the regulation of ryanodine receptors (RyRs) and inositol 1,4,5-trisphosphate receptors (IP3Rs), both tetrameric intracellular Ca2+-release channels. Whereas the amino acid sequences responsible for FKBP12 binding to RyRs are conserved in IP3Rs, FKBP12 binding to IP3Rs has been questioned and could not be observed in various experimental models. Nevertheless, conservation of these residues in the different IP3R isoforms and during evolution suggested that they could harbour an important regulatory site critical for IP3R-channel function. Recently, it has become clear that in IP3Rs, this site was targeted by B-cell lymphoma 2 (Bcl-2) via its Bcl-2 homology (BH)4 domain, thereby dampening IP3R-mediated Ca2+ flux and preventing pro-apoptotic Ca2+ signalling. Furthermore, vice versa, the presence of the corresponding site in RyRs implied that Bcl-2 proteins could associate with and regulate RyR channels. Recently, the existence of endogenous RyR–Bcl-2 complexes has been identified in primary hippocampal neurons. Like for IP3Rs, binding of Bcl-2 to RyRs also involved its BH4 domain and suppressed RyR-mediated Ca2+ release. We therefore propose that the originally identified FKBP12-binding site in IP3Rs is a region critical for controlling IP3R-mediated Ca2+ flux by recruiting Bcl-2 rather than FKBP12. Although we hypothesize that anti-apoptotic Bcl-2 proteins, but not FKBP12, are the main physiological inhibitors of IP3Rs, we cannot exclude that Bcl-2 could help engaging FKBP12 (or other FKBP isoforms) to the IP3R, potentially via calcineurin.

scholarly journals Regulation of cadherin dimerization by chemical fragments as a trigger to inhibit cell adhesion

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Akinobu Senoo ◽  
Sho Ito ◽  
Satoru Nagatoishi ◽  
Yutaro Saito ◽  
Go Ueno ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Hydrogen Bonds ◽  
Small Molecules ◽  
Small Molecule ◽  
Protein Interactions ◽  
Therapeutic Potential ◽  
Protein Complexes ◽  
Protein Protein Interactions ◽  
Specific Chemical ◽  
Stepwise Assembly

AbstractMany cadherin family proteins are associated with diseases such as cancer. Since cell adhesion requires homodimerization of cadherin molecules, a small-molecule regulator of dimerization would have therapeutic potential. Herein, we describe identification of a P-cadherin-specific chemical fragment that inhibits P-cadherin-mediated cell adhesion. Although the identified molecule is a fragment compound, it binds to a cavity of P-cadherin that has not previously been targeted, indirectly prevents formation of hydrogen bonds necessary for formation of an intermediate called the X dimer and thus modulates the process of X dimerization. Our findings will impact on a strategy for regulation of protein-protein interactions and stepwise assembly of protein complexes using small molecules.

scholarly journals The interactome: Predicting the protein-protein interactions in cells

2009 ◽  
Vol 14 (1) ◽  
pp. 1-22 ◽  
Author(s):  
Dariusz Plewczyński ◽  
Krzysztof Ginalski
Keyword(s):  
Protein Interactions ◽  
Three Dimensional ◽  
Short Review ◽  
Amino Acid Sequences ◽  
Protein Protein Interactions ◽  
Structure Information ◽  
Cellular Processes ◽  
Molecular Machinery ◽  
Genome Scale ◽  
In Cells

AbstractThe term Interactome describes the set of all molecular interactions in cells, especially in the context of protein-protein interactions. These interactions are crucial for most cellular processes, so the full representation of the interaction repertoire is needed to understand the cell molecular machinery at the system biology level. In this short review, we compare various methods for predicting protein-protein interactions using sequence and structure information. The ultimate goal of those approaches is to present the complete methodology for the automatic selection of interaction partners using their amino acid sequences and/or three dimensional structures, if known. Apart from a description of each method, details of the software or web interface needed for high throughput prediction on the whole genome scale are also provided. The proposed validation of the theoretical methods using experimental data would be a better assessment of their accuracy.

scholarly journals Nucleic Acid Binding by Mason-Pfizer Monkey Virus CA Promotes Virus Assembly and Genome Packaging

2016 ◽  
Vol 90 (9) ◽  
pp. 4593-4603 ◽  
Author(s):  
Tibor Füzik ◽  
Růžena Píchalová ◽  
Florian K. M. Schur ◽  
Karolína Strohalmová ◽  
Ivana Křížová ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Protein Interactions ◽  
Viral Genome ◽  
Virus Assembly ◽  
Protein Protein Interactions ◽  
Genome Packaging ◽  
Particle Assembly ◽  
Nuclear Trafficking ◽  
Virus Particles ◽  
Gag Polyprotein

ABSTRACTThe Gag polyprotein of retroviruses drives immature virus assembly by forming hexameric protein lattices. The assembly is primarily mediated by protein-protein interactions between capsid (CA) domains and by interactions between nucleocapsid (NC) domains and RNA. Specific interactions between NC and the viral RNA are required for genome packaging. Previously reported cryoelectron microscopy analysis of immature Mason-Pfizer monkey virus (M-PMV) particles suggested that a basic region (residues RKK) in CA may serve as an additional binding site for nucleic acids. Here, we have introduced mutations into the RKK region in both bacterial and proviral M-PMV vectors and have assessed their impact on M-PMV assembly, structure, RNA binding, budding/release, nuclear trafficking, and infectivity usingin vitroandin vivosystems. Our data indicate that the RKK region binds and structures nucleic acid that serves to promote virus particle assembly in the cytoplasm. Moreover, the RKK region appears to be important for recruitment of viral genomic RNA into Gag particles, and this function could be linked to changes in nuclear trafficking. Together these observations suggest that in M-PMV, direct interactions between CA and nucleic acid play important functions in the late stages of the viral life cycle.IMPORTANCEAssembly of retrovirus particles is driven by the Gag polyprotein, which can self-assemble to form virus particles and interact with RNA to recruit the viral genome into the particles. Generally, the capsid domains of Gag contribute to essential protein-protein interactions during assembly, while the nucleocapsid domain interacts with RNA. The interactions between the nucleocapsid domain and RNA are important both for identifying the genome and for self-assembly of Gag molecules. Here, we show that a region of basic residues in the capsid protein of the betaretrovirus Mason-Pfizer monkey virus (M-PMV) contributes to interaction of Gag with nucleic acid. This interaction appears to provide a critical scaffolding function that promotes assembly of virus particles in the cytoplasm. It is also crucial for packaging the viral genome and thus for infectivity. These data indicate that, surprisingly, interactions between the capsid domain and RNA play an important role in the assembly of M-PMV.

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