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Visualización de las modificaciones químicas en la estructura del ribosoma 80S humano
S Kundhavai Natchiar1,2,3,4,5, Alexander G Myasnikov1,2,3,4,5, Hanna Kratzat1,2,3,4,5
1Centre for Integrative Biology (CBI), Department of Integrated Structural Biology, IGBMC, CNRS, Inserm, Université de Strasbourg, 1 rue Laurent Fries, 67404 Illkirch, France.
Nature
|November 17, 2017
Resumen
Las modificaciones del ARN ribosomal humano (ARNr) se visualizan en 3D, revelando su papel en la síntesis de proteínas y las enfermedades. Esta visión estructural ayuda a comprender el cáncer y a desarrollar nuevos fármacos dirigidos a los ribosomas.
Área de la Ciencia:
- Biología molecular
- Biología estructural
- La bioquímica
Sus antecedentes:
- Las modificaciones químicas del ARN ribosomal humano (ARNr) ocurren durante la biogénesis y están relacionadas con la desregulación de la síntesis de proteínas en enfermedades como el cáncer.
- Las funciones estructurales y funcionales precisas de estas modificaciones del ARNr siguen siendo en gran medida desconocidas.
Objetivo del estudio:
- Para visualizar más de 130 modificaciones individuales de ARNr dentro de la estructura tridimensional del ribosoma humano.
- Para aclarar la importancia estructural y funcional de estas modificaciones en los ribosomas humanos.
Principales métodos:
- Análisis estructural de alta resolución del ribosoma humano 80S.
- Visualización y mapeo de más de 130 modificaciones individuales de ARNr.
Principales resultados:
- Visualización detallada de más de 130 modificaciones individuales de ARNr en la estructura tridimensional del ribosoma humano.
- Identificación de modificaciones universalmente conservadas, específicas de los eucariotas y específicas de los humanos, con sitios únicos que forman una cáscara extendida y estabilizadora en comparación con los ribosomas bacterianos.
- Asociación de varias modificaciones con los sitios de unión de antibióticos dirigidos a los ribosomas y con estados degenerados relacionados con el cáncer, incluidas las cetoalquilaciones.
Conclusiones:
- La estructura de alta resolución del ribosoma humano 80S proporciona una base para comprender el papel de las modificaciones epigenéticas del ARNr en las enfermedades humanas.
- Estos hallazgos sugieren nuevas estrategias terapéuticas, incluido el diseño de inhibidores selectivos y medicamentos dirigidos a los ribosomas humanos.
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