REVISTA

La estructura del canal iónico TRPA1 sugiere mecanismos reguladores

Descripción: Utilizamos la crioscopía electrónica de partículas individuales para determinar la estructura de TRPA1 humano. Se revelan varias características inesperadas. Estos hallazgos proporcionan nuevos conocimientos sobre los mecanismos de regulación de TRPA1 y establecen un modelo para el diseño de analgésicos y antiinflamatorios

TITULO FUENTE ORIGINAL:

Structure of the TRPA1 ion channel suggests regulatory mechanisms

AUTORES:

Paulsen CE, Armache JP, Gao Y, Cheng Y, Julius D

REVISTA ABREV.:

Nature

AÑO:

2015

REFERENCIA:

520(7548):511-7

DOI:

10.1038/nature14367

RESUMEN ORIGINAL:

The TRPA1 ion channel (also known as the wasabi receptor) is a detector of noxious chemical agents encountered in our environment or produced endogenously during tissue injury or drug metabolism. These include a broad class of electrophiles that activate the channel through covalent protein modification. TRPA1 antagonists hold potential for treating neurogenic inflammatory conditions provoked... + Leer más

The TRPA1 ion channel (also known as the wasabi receptor) is a detector of noxious chemical agents encountered in our environment or produced endogenously during tissue injury or drug metabolism. These include a broad class of electrophiles that activate the channel through covalent protein modification. TRPA1 antagonists hold potential for treating neurogenic inflammatory conditions provoked or exacerbated by irritant exposure. Despite compelling reasons to understand TRPA1 function, structural mechanisms underlying channel regulation remain obscure. Here we use single-particle electron cryo- microscopy to determine the structure of full-length human TRPA1 to ∼4 Å resolution in the presence of pharmacophores, including a potent antagonist. Several unexpected features are revealed, including an extensive coiled-coil assembly domain stabilized by polyphosphate co-factors and a highly integrated nexus that converges on an unpredicted transient receptor potential (TRP)-like allosteric domain. These findings provide new insights into the mechanisms of TRPA1 regulation, and establish a blueprint for structure-based design of analgesic and anti-inflammatory agents

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Enlace al pdf de acceso libre: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC[...]