Video Experimental Relacionado
Updated: Jul 14, 2025
06:03
Use of Viral Entry Assays and Molecular Docking Analysis for the Identification of Antiviral Candidates against Coxsackievirus A16
Published on: July 15, 2019
8.0K
Modos de unión específicos de la clase de los vertebrados del receptor del alfavirus MXRA8
Ofer Zimmerman1, Maxwell I Zimmerman2, Saravanan Raju2
1Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA.
Cell
|October 7, 2023
Resumen
El MXRA8 aviar se une a los alfavirus como Sindbis y WEEV, a diferencia del MXRA8 de los mamíferos. Un nuevo receptor quimérico neutraliza diversas infecciones de alfavirus, allanando el camino para los inhibidores de amplio espectro.
Área de la Ciencia:
- Virología
- Biología estructural
- Inmunología
Sus antecedentes:
- MXRA8 es un receptor conocido para el virus de la chikungunya (CHIKV) y otros alfavirus en mamíferos.
- El MXRA8 de mamíferos no se une a los alfavirus con los reservorios aviares que infectan a los humanos.
Objetivo del estudio:
- Investigar el papel del MXRA8 aviar en la unión al alfavirus.
- Para aclarar la base estructural de las interacciones entre alfavirus y MXRA8.
- Para desarrollar un inhibidor de alfavirus de amplio espectro.
Principales métodos:
- Análisis estructural del pato MXRA8 complejado con WEEV.
- Comparación de los modos de unión entre MXRA de aves y mamíferos8.
- Generación y ensayo de un receptor de señuelo quimérico MXRA8.
Principales resultados:
- El MXRA8 de las aves, pero no el MXRA8 de los mamíferos, actúa como receptor de los alfavirus reservorios de las aves (por ejemplo, Sindbis, WEEV).
- Se observaron modos de unión distintos: el MXRA8 de los mamíferos se une al CHIKV E1 y E2, mientras que el MXRA8 de las aves sólo se une al WEEV E1.
- Un receptor señuelo quimérico aviar-mamífero MXRA8 demostró la neutralización in vitro e in vivo de múltiples alfavirus.
Conclusiones:
- Los alfavirus exhiben mecanismos de unión distintos a los receptores MXRA8 de diferentes clases de vertebrados.
- Comprender estos modos de unión diferenciales es crucial para desarrollar terapias antivirales efectivas de amplio espectro.
Videos de Conceptos Relacionados
01:15Receptor Downregulation in MVBs
2.1K
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
2.1K
01:27Transducer Mechanism: Enzyme-Linked Receptors
2.5K
Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Major types that are helpful drug targets include:
2.5K
01:30Ligand-Gated Ion Channel Receptor: Gating Mechanism
2.3K
Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
2.3K
01:49Conserved Binding Sites
4.2K
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
4.2K
00:49Ligand Binding and Linkage
4.8K
Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked. In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence...
4.8K
01:30Transducer Mechanism: G Protein–Coupled Receptors
2.1K
G Protein–Coupled Receptors (GPCRs) are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to various stimuli. GPCRs regulate critical physiological pathways and are excellent drug targets for treating diseases such as diabetes, cancer, obesity, depression, or Alzheimer's. Nearly 35% of approved drugs implement their therapeutic effects by selectively interacting with specific GPCRs.
GPCRs are also called heptahelical,...
GPCRs are also called heptahelical,...
2.1K