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PMID: 12651956 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Domain organization of the type 1 inositol 1,4,5-trisphosphate receptor as revealed by single-particle analysis.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 100 ·No. 7 ·2003-04-01 ·Pages 3936-41

da Fonseca PC, Morris SA, Nerou EP, Taylor CW, Morris EP

Abstract

The inositol 1,4,5-trisphosphate receptor (IP(3)R) is a tetrameric intracellular Ca(2+) channel, which mediates the release of Ca(2+) from the endoplasmic reticulum in response to many different extracellular stimuli. We present a 3D structure of the type 1 IP(3)R obtained by electron microscopy and single-particle analysis that reveals its domain organization. The IP(3)R has a flower-like appearance with fourfold symmetry and is made up of three distinct domains connected by slender links. By relating the organization of the structural domains to secondary-structure predictions and biochemical data we develop a model in which structural domains are mapped onto the amino acid sequence to deduce the location of the channel region and the cytoplasmic inositol 1,4,5-trisphosphate-binding and modulatory subdomains. The structure of the IP(3)R is compared with that of other tetrameric cation channels. The channel domain is similar in size and shape to its counterparts in the ryanodine receptor and the Shaker voltage-gated K(+) channel.

MeSH Terms
Animals Calcium Channels/chemistry,isolation & purification,ultrastructure Cell Membrane/chemistry Cerebellum/chemistry Cytoplasm/ultrastructure Image Processing, Computer-Assisted Inositol 1,4,5-Trisphosphate Receptors Ion Channels/chemistry,isolation & purification Microscopy, Electron Protein Conformation Protein Structure, Secondary Protein Subunits/chemistry,isolation & purification Receptors, Cytoplasmic and Nuclear/chemistry,isolation & purification,ultrastructure
Chemicals
Calcium Channels Inositol 1,4,5-Trisphosphate Receptors Ion Channels Protein Subunits Receptors, Cytoplasmic and Nuclear
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
da Fonseca Paula C A
Biomedical Sciences Division, Sir Alexander Fleming Building, Imperial College of Science Technology and Medicine, London SW7 2AZ, United Kingdom.
Morris Stephen A
Nerou Edmund P
Taylor Colin W
Morris Edward P
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0536251100
Published
2003-04-01
Epub
2003-00-21
Pages
3936-41
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC153026
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.0536251100 PMC Full Text View journal details
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