Journal
JOURNAL OF MOLECULAR BIOLOGY
Volume 336, Issue 1, Pages 155-164Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jmb.2003.11.024
Keywords
single-particle analysis; IP3 receptor; Ca2+ channel; ligand-gated channel; cryo-electron microscopy
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Calcium concentrations are strictly regulated in all biological cells, and one of the key molecules responsible for this regulation is the inositol 1,4,5-trisphosphate receptor, which was known to form a homotetrameric Ca2+ channel in the endoplasmic reticulum. The receptor is involved in neuronal transmission via Ca2+ signaling and for many other functions that relate to morphological and physiological processes in living organisms. We analysed the three-dimensional structure of the ligand-free form of the receptor based on a single-particle technique using an originally developed electron microscope equipped with a helium-cooled specimen stage and an automatic particle picking system. We propose a model that explains the complex mechanism for the regulation of Ca2+ release by co-agonists,Ca2+, inositol 1,4,5 tri-phosphate based on the structure of multiple internal cavities and a porous balloon-shaped cytoplasmic domain containing a prominent L-shaped density which was assigned by the X-ray structure of the inositol 1,4,5-trisphosphate binding domain. (C) 2003 Elsevier Ltd. All rights reserved.
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