Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Más filtros

Bases de datos
Tipo del documento
Intervalo de año de publicación
1.
J Biol Chem ; 289(15): 10660-10667, 2014 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-24596090

RESUMEN

The transmission of infectious prions into different host species requires compatible prion protein (PrP) primary structures, and even one heterologous residue at a pivotal position can block prion infection. Mapping the key amino acid positions that govern cross-species prion conversion has not yet been possible, although certain residue positions have been identified as restrictive, including residues in the ß2-α2 loop region of PrP. To further define how ß2-α2 residues impact conversion, we investigated residue substitutions in PrP(C) using an in vitro prion conversion assay. Within the ß2-α2 loop, a tyrosine residue at position 169 is strictly conserved among mammals, and transgenic mice expressing mouse PrP having the Y169G, S170N, and N174T substitutions resist prion infection. To better understand the structural requirements of specific residues for conversion initiated by mouse prions, we substituted a diverse array of amino acids at position 169 of PrP. We found that the substitution of glycine, leucine, or glutamine at position 169 reduced conversion by ∼ 75%. In contrast, replacing tyrosine 169 with either of the bulky, aromatic residues, phenylalanine or tryptophan, supported efficient prion conversion. We propose a model based on a requirement for tightly interdigitating complementary amino acid side chains within specific domains of adjacent PrP molecules, known as "steric zippers," to explain these results. Collectively, these studies suggest that an aromatic residue at position 169 supports efficient prion conversion.


Asunto(s)
Proteínas PrPC/química , Priones/química , Priones/genética , Tirosina/química , Amiloide/química , Animales , Sistema Libre de Células , Ratones , Mutagénesis Sitio-Dirigida , Mutación , Enfermedades Neurodegenerativas/genética , Enfermedades por Prión/genética , Proteínas Priónicas , Unión Proteica , Estructura Terciaria de Proteína
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA