Publications
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Synthesis of Conformationally Restricted alfa-Helix Mimics as Rev Multimerization Inhibitors and Synthesis of Functionalised 1-Hydroxypyrazin-2(1H)-one Scaffolds as Potential Integrase Inhibitors. KU Leuven
With the continued emergence of drug-resistant strains of the Human Immunodeficiency Virus (HIV), Highly Active Anti-retroviral Therapy (HAART) may prove to be only a stopgap measure. Consequently, more efforts must be made in the development of new therapies and new targets that would complement existing strategies and increase the barrier to the evolution of resistant strains of HIV-1.In the HIV life cycle, each and every step is important for ...
Computational investigation of the HIV-1 Rev multimerization using molecular dynamics simulations and binding free energy calculations KU Leuven
The HIV Rev protein mediates the nuclear export of viral mRNA, and is thereby essential for the production of late viral proteins in the replication cycle. Rev forms a large organized multimeric protein-protein complex for proper functioning. Recently, the three-dimensional structures of a Rev dimer and tetramer have been resolved and provide the basis for a thorough structural analysis of the binding interaction. Here, molecular dynamics (MD) ...
An Intrabody Based on a Llama Single-domain Antibody Targeting the N-terminal alpha-Helical Multimerization Domain of HIV-1 Rev Prevents Viral Production Vrije Universiteit Brussel KU Leuven
The human immunodeficiency virus, type 1 (HIV-1)-encoded Rev protein is essential for the expression of late viral mRNAs. Rev forms a large organized multimeric protein-protein complex on the Rev response element of these viral mRNA species and transports them from the nucleus to the cytoplasm, exploiting the CRM1-mediated cellular machinery. Here we report the selection of a nanobody, derived from a llama heavy-chain only antibody, that ...
An intrabody based on a llama single-domain antibody targeting the N-terminal alpha-helical multimerization domain of HIV-1 REV prevents viral production KU Leuven
The HIV-1-encoded Rev protein is essential for the expression of late viral mRNAs. Rev forms a large organized multimeric protein-protein complex on the Rev response element of these viral mRNA species and transports them from the nucleus to the cytoplasm exploiting the CRM1-mediated cellular machinery. Here we report the selection of a nanobody, derived from a llama heavy-chain only antibody, that efficiently blocks the assembly of Rev ...
Proteolysis and multimerization regulate signaling along the two-component regulatory system AdeRS Ghent University
Bacterial two-component regulatory systems are ubiquitous environment-sensing signal transducers involved in pathogenesis and antibiotic resistance. The Acinetobacter baumannii two-component regulatory system AdeRS is made up of a sensor histidine kinase AdeS and a cognate response regulator AdeR, which together reduce repression of the multidrug-resistant efflux pump AdeABC. Herein we demonstrate that an N-terminal intrinsically disordered tail ...
A new role for Escherichia coli DsbC protein in protection against oxidative stress Vrije Universiteit Brussel
We report a new function for Escherichia coli DsbC, a protein best known for disulfide bond isomerization in the periplasm. We found that DsbC regulates the redox state of the single cysteine of the L-arabinose-binding protein AraF. This cysteine, which can be oxidized to a sulfenic acid, mediates the formation of a disulfide-linked homodimer under oxidative stress conditions, preventing L-arabinose binding. DsbC, unlike the homologous ...
Mapping the Binding Interface between an HIV-1 Inhibiting Intrabody and the Viral Protein Rev Vrije Universiteit Brussel KU Leuven
HIV-1 Rev is the key protein in the nucleocytoplasmic export and expression of the late viral mRNAs. An important aspect for its function is its ability to multimerize on these mRNAs. We have recently identified a llama single-domain antibody (Nb190) as the first inhibitor targeting the Rev multimerization function in cells. This nanobody is a potent intracellular antibody that efficiently inhibits HIV-1 viral production. In order to gain ...
A fijivirus major viroplasm protein shows RNA-Stimulated ATPase activity by adopting pentameric and hexameric assemblies of dimers University of Antwerp
Fijiviruses replicate and package their genomes within viroplasms in a process involving RNA-RNA and RNA-protein interactions. Here, we demonstrate that the 24 C-terminal residues (C-arm) of the P9-1 major viroplasm protein of the mal de Río Cuarto virus (MRCV) are required for its multimerization and the formation of viroplasm-like structures. Using an integrative structural approach, the C-arm was found to be dispensable for P9-1 dimer ...
Probing effects of the SARS-CoV-2 E protein on membrane curvature and intracellular calcium KU Leuven
SARS-CoV-2 contains four structural proteins in its genome. These proteins aid in the assembly and budding of new virions at the ER-Golgi intermediate compartment (ERGIC). Current fundamental research efforts largely focus on one of these proteins - the spike (S) protein. Since successful antiviral therapies are likely to target multiple viral components, there is considerable interest in understanding the biophysical role of its other ...