Gating machinery of InsP3R channels revealed by electron cryomicroscopy
- Autores: Guizhen Fan, Matthew L. Baker, Zhao Wang, Mariah R. Baker, Pavel A. Sinyagovskiy, Wah Chiu, Steven J. Ludtke, Irina I. Serysheva
- Localización: Nature: International weekly journal of science, ISSN 0028-0836, Vol. 527, Nº 7578, 2015, págs. 336-341
- Idioma: inglés
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Resumen
Inositol-1,4,5-trisphosphate receptors (InsP3Rs) are ubiquitous ion channels responsible for cytosolic Ca2+ signalling and essential for a broad array of cellular processes ranging from contraction to secretion, and from proliferation to cell death. Despite decades of research on InsP3Rs, a mechanistic understanding of their structure–function relationship is lacking. Here we present the first, to our knowledge, near-atomic (4.7 Å) resolution electron cryomicroscopy structure of the tetrameric mammalian type 1 InsP3R channel in its apo-state. At this resolution, we are able to trace unambiguously ~85% of the protein backbone, allowing us to identify the structural elements involved in gating and modulation of this 1.3-megadalton channel. Although the central Ca2+-conduction pathway is similar to other ion channels, including the closely related ryanodine receptor, the cytosolic carboxy termini are uniquely arranged in a left-handed [alpha]-helical bundle, directly interacting with the amino-terminal domains of adjacent subunits. This configuration suggests a molecular mechanism for allosteric regulation of channel gating by intracellular signals.
