Two-state conformational changes in inositol 1,4,5-trisphosphate receptor regulated by calcium

Kozo Hamada, Tomoko Miyata, Kouta Mayanagi, Junji Hirota, Katsuhiko Mikoshiba

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

Inositol 1,4,5-trisphosphate receptor (IP3R) is a highly controlled calcium (Ca2+) channel gated by inositol 1,4,5-trisphosphate (IP3). Multiple regulators modulate IP3-triggered pore opening by binding to discrete allosteric sites within IP3R. Accordingly we have postulated that these regulators structurally control ligand gating behavior; however, no structural evidence has been available. Here we show that Ca2+, the most pivotal regulator, induced marked structural changes in the tetrameric IP3R purified from mouse cerebella. Electron microscopy of the IP3R particles revealed two distinct structures with 4-fold symmetry: a windmill structure and a square structure. Ca2+ reversibly promoted a transition from the square to the windmill with relocations of four peripheral IP3-binding domains, assigned by binding to heparin-gold. Ca2+-dependent susceptibilities to limited digestion strongly support the notion that these alterations exist. Thus, Ca2+ appeared to regulate IP3 gating activity through the rearrangement of functional domains.

Original languageEnglish
Pages (from-to)21115-21118
Number of pages4
JournalJournal of Biological Chemistry
Volume277
Issue number24
DOIs
Publication statusPublished - Jun 14 2002

Fingerprint

Allosteric Site
Inositol 1,4,5-Trisphosphate Receptors
Inositol 1,4,5-Trisphosphate
Relocation
Calcium Channels
Gold
Cerebellum
Electron microscopy
Heparin
Digestion
Electron Microscopy
Ligands
Calcium

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Two-state conformational changes in inositol 1,4,5-trisphosphate receptor regulated by calcium. / Hamada, Kozo; Miyata, Tomoko; Mayanagi, Kouta; Hirota, Junji; Mikoshiba, Katsuhiko.

In: Journal of Biological Chemistry, Vol. 277, No. 24, 14.06.2002, p. 21115-21118.

Research output: Contribution to journalArticle

Hamada, Kozo ; Miyata, Tomoko ; Mayanagi, Kouta ; Hirota, Junji ; Mikoshiba, Katsuhiko. / Two-state conformational changes in inositol 1,4,5-trisphosphate receptor regulated by calcium. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 24. pp. 21115-21118.
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