Non-structural (NS) proteins of dengue virus (DENV) are important for viral replication. There are four membrane proteins that are coded by viral genome. NS2B was shown to be one of the membrane proteins and its main function was confirmed to regulate viral protease activity. Its membrane topology is still not known because only few studies have been conducted to understand its structure. Here we report the determination of membrane topology of NS2B from DENV serotype 4 using NMR spectroscopy. NS2B of DENV4 was expressed and purified in detergent micelles. The secondary structure of NS2B was first defined based on backbone chemical resonance assignment. Four helices were identified in NS2B. The membrane topology of NS2B was defined based on relaxation analysis and paramagnetic relaxation enhancement experiments. The last three helices were shown to be more stable than the first helix. The NS3 protease cofactor region between α2 and α3 is highly dynamic. Our results will be useful for further structural and functional analysis of NS2B.
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http://dx.doi.org/10.1016/j.bbamem.2015.06.010 | DOI Listing |
Nat Chem
January 2025
Institute of Bioengineering, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.
Protein catalysis and allostery require the atomic-level orchestration and motion of residues and ligand, solvent and protein effector molecules. However, the ability to design protein activity through precise protein-solvent cooperative interactions has not yet been demonstrated. Here we report the design of 14 membrane receptors that catalyse G protein nucleotide exchange through diverse engineered allosteric pathways mediated by cooperative networks of intraprotein, protein-ligand and -solvent molecule interactions.
View Article and Find Full Text PDFNeurotherapeutics
January 2025
Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Chile. Electronic address:
Acute brain injuries (ABIs) encompass a broad spectrum of primary injuries such as ischemia, hypoxia, trauma, and hemorrhage that converge into secondary injury where some mechanisms show common determinants. In this regard, astroglial connexin and pannexin channels have been shown to play an important role. These channels are transmembrane proteins sharing similar topology and form gateways between adjacent cells named gap junctions (GJs) and pores into unopposed membranes named hemichannels (HCs).
View Article and Find Full Text PDFACS Infect Dis
January 2025
Programa de Pós-Graduação em Biotecnologia, Universidade Católica Dom Bosco, Campo Grande, Mato Grosso do Sul 79117-900, Brazil.
Plants provide an abundant source of potential therapeutic agents, including a diverse array of compounds, such as cyclotides, which are peptides known for their antimicrobial activity. Cyclotides are multifaceted molecules with a wide range of biological activities. Their unique topology forms a head-to-tail cyclic structure reinforced by a cysteine knot, which confers chemical and thermal stability.
View Article and Find Full Text PDFCommun Biol
January 2025
Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Prevention, Suzhou Medical College, Soochow University, Suzhou, 215123, China.
Positively charged residues are commonly located near the cytoplasm-membrane interface, which is known as the positive-inside rule in membrane topology. The mechanism underlying the function of these charged residues remains poorly understood. Herein, we studied the function of cytoplasmic residues in corin, a type II transmembrane serine protease in cardiovascular biology.
View Article and Find Full Text PDFInt J Pharm
January 2025
Drug Product and Device Technologies, BioMarin Pharmaceutical, Inc, Novato, CA 94949, USA.
Glass delamination is a gradual process that may not become apparent until late in storage. Over the past three decades, it has been a leading cause of drug product recalls due to glass particulate contamination. The appearance of glass particles in the solution marks the final stage of glass delamination.
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