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PAR-CliP - A Method to Identify Transcriptome-wide the Binding Sites of RNA Binding Proteins

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Published on: July 2, 2010

Reconocimiento del ARN poliadenilato por la proteína de unión al poli (A)

R C Deo¹, J B Bonanno, N Sonenberg

¹Laboratories of Molecular Biophysics, The Rockefeller University, New York, New York 10021, USA.

|September 28, 1999

Resumen

Se reveló la estructura de la proteína humana de unión a poliA (PABP) unida al ARNm, mostrando cómo reconoce la cola poliA. Este hallazgo ofrece información sobre la traducción y la estabilidad del ARNm en eucariotas.

Área de la Ciencia:

Biología Molecular Biología Molecular
Biología Estructural Biología estructural.
La bioquímica es la bioquímica.

Sus antecedentes:

La proteína de unión poli-A (PABP, por sus siglas en inglés) es esencial para la expresión génica eucariota.
PABP se une a la cola 3' del ARNm poli, influyendo en la traducción y la estabilidad del ARNm.
Comprender la estructura de PABP es clave para aclarar sus funciones regulatorias.

Objetivo del estudio:

Determinar la estructura cocristalina del PABP humano con su ligando de ARN.
Para dilucidar las interacciones moleculares entre PABP y la cola poli (A).
Proporcionar una base estructural para el papel del PABP en la traducción y el metabolismo del ARNm.

Principales métodos:

Cristalografía de rayos X con una resolución de 2.6 A.
Cocristalización del PABP humano (dominios RRM1/2) con el ARN poliadenilato.
Análisis estructural y modelado molecular.

Principales resultados:

La estructura revela un canal continuo de unión al ARN formado por los dominios RRM1/2 de PABP.
El ARN poliadenilato adopta una conformación extendida dentro del fondo de unión.
Los contactos específicos entre los residuos conservados del motivo RNP y las bases de adenina median el reconocimiento del ARN.
Una superficie hidrofóbica/ácida conservada en PABP RRM1/2 sugiere interacciones con otras proteínas.

Conclusiones:

La estructura determinada proporciona un mecanismo molecular detallado para el reconocimiento por parte de PABP de la cola poli-A.
Esta visión estructural es crucial para comprender las funciones de la PABP en la iniciación de la traducción y la desintegración del ARNm.
La superficie conservada puede mediar interacciones con factores de traducción, ofreciendo objetivos para estudios regulatorios.

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