Video Experimental Relacionado
Updated: Sep 6, 2025
13:00
Engineering Antiviral Agents via Surface Plasmon Resonance
Published on: June 14, 2022
2.4K
Cambiar las restricciones mutacionales en el dominio de unión al receptor del SARS-CoV-2 durante la evolución viral
Tyler N Starr1, Allison J Greaney1,2,3, William W Hannon1,4
1Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Science (New York, N.Y.)
|June 28, 2022
Resumen
Las variantes del SARS-CoV-2 evolucionan a través de mutaciones en el dominio de unión al receptor (RBD) de la proteína del pico. Estos cambios, influenciados por la epistasis, dan forma a la evolución viral y al escape de anticuerpos, impactando las cepas futuras como Omicron.
Área de la Ciencia:
- Virología
- Biología molecular
- La genética
Sus antecedentes:
- Las variantes del coronavirus 2 del síndrome respiratorio agudo severo (SARS-CoV-2) muestran sustituciones del dominio de unión al receptor de picos (RBD) que afectan la unión al ACE2 y el reconocimiento de anticuerpos.
- Estas sustituciones pueden influir en la evolución viral futura a través de la epistasis, donde las mutaciones en un sitio alteran los efectos de las mutaciones en otros sitios.
Objetivo del estudio:
- Investigar el papel de la epistasis en la configuración de la evolución del SARS-CoV-2.
- Para medir el impacto de todas las mutaciones de un solo aminoácido en los RBD de varias variantes del SARS-CoV-2 (Wuhan-Hu-1, Alpha, Beta, Delta, Eta) en la unión al ACE2.
Principales métodos:
- Se empleó un escaneo mutativo profundo para evaluar los efectos de todas las sustituciones de aminoácidos individuales en las RBD de las variantes específicas de SARS-CoV-2.
- El análisis se centró en los cambios en la afinidad de unión al receptor de la enzima convertidora de angiotensina 2 (ACE2) en humanos.
Principales resultados:
- Las sustituciones específicas, especialmente Asn501Tyr (N501Y), indujeron desplazamientos epistáticos, alterando los efectos de las mutaciones en otros sitios.
- Estos cambios epistáticos se observaron para facilitar los cambios evolutivos posteriores, incluidas las mutaciones de escape de anticuerpos observadas en la variante Omicron.
- Los efectos epistáticos fueron evidentes a pesar de la estructura general conservada de la RBD.
Conclusiones:
- La epistasis juega un papel crucial en la trayectoria evolutiva del SARS-CoV-2, influyendo en la aparición de variantes con propiedades de unión y evasión inmunológica alteradas.
- Comprender estas relaciones de secuencia-función en el RBD es vital para interpretar la evolución viral en curso y predecir futuras adaptaciones del SARS-CoV-2.
Más Videos Relacionados
Videos de Conceptos Relacionados
00:36Viral Mutations
32.8K
A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material...
32.8K
02:28Leaky Scanning
5.2K
During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA. Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.2K
01:49Conserved Binding Sites
4.3K
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...
4.3K
01:30Point and Frameshift Mutations
72
Point mutations are genetic alterations involving the change of a single nucleotide base pair in DNA. Depending on how the alteration affects protein synthesis, they can lead to various consequences.Point mutations fall into the following types:Silent mutations occur when a nucleotide change does not alter the amino acid sequence due to the redundancy of the genetic code. For instance, changing ACC to ACA still encodes threonine, leaving the protein function unaffected. This occurs because...
72
02:05Gene Evolution - Fast or Slow?
7.3K
The genomes of eukaryotes are punctuated by long stretches of sequence which do not code for proteins or RNAs. Although some of these regions do contain crucial regulatory sequences, the vast majority of this DNA serves no known function. Typically, these regions of the genome are the ones in which the fastest change, in evolutionary terms, is observed, because there is typically little to no selection pressure acting on these regions to preserve their sequences.
In contrast, regions which code...
In contrast, regions which code...
7.3K
01:05Single Nucleotide Polymorphisms-SNPs
15.8K
A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
15.8K