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Structure paper

TitleStructural basis for activation and gating of IP receptors.
Journal, issue, pagesNat Commun, Vol. 13, Issue 1, Page 1408, Year 2022
Publish dateMar 17, 2022
AuthorsEmily A Schmitz / Hirohide Takahashi / Erkan Karakas /
PubMed AbstractA pivotal component of the calcium (Ca) signaling toolbox in cells is the inositol 1,4,5-triphosphate (IP) receptor (IPR), which mediates Ca release from the endoplasmic reticulum (ER), controlling ...A pivotal component of the calcium (Ca) signaling toolbox in cells is the inositol 1,4,5-triphosphate (IP) receptor (IPR), which mediates Ca release from the endoplasmic reticulum (ER), controlling cytoplasmic and organellar Ca concentrations. IPRs are co-activated by IP and Ca, inhibited by Ca at high concentrations, and potentiated by ATP. However, the underlying molecular mechanisms are unclear. Here we report cryo-electron microscopy (cryo-EM) structures of human type-3 IPR obtained from a single dataset in multiple gating conformations: IP-ATP bound pre-active states with closed channels, IP-ATP-Ca bound active state with an open channel, and IP-ATP-Ca bound inactive state with a closed channel. The structures demonstrate how IP-induced conformational changes prime the receptor for activation by Ca, how Ca binding leads to channel opening, and how ATP modulates the activity, providing insights into the long-sought questions regarding the molecular mechanism underpinning receptor activation and gating.
External linksNat Commun / PubMed:35301323 / PubMed Central
MethodsEM (single particle)
Resolution3.2 - 3.8 Å
Structure data

25667

7t3p

EMDB-25667, PDB-7t3p:
IP3 and ATP bound type 3 IP3 receptor in the pre-active A state
Method: EM (single particle) / Resolution: 3.2 Å

25668

7t3q

EMDB-25668, PDB-7t3q:
IP3 and ATP bound type 3 IP3 receptor in the pre-active B state
Method: EM (single particle) / Resolution: 3.3 Å

25669

7t3r

EMDB-25669, PDB-7t3r:
IP3 and ATP bound type 3 IP3 receptor in the pre-active C state
Method: EM (single particle) / Resolution: 3.4 Å

25670

7t3t

EMDB-25670, PDB-7t3t:
IP3, ATP, and Ca2+ bound type 3 IP3 receptor in the active state
Method: EM (single particle) / Resolution: 3.8 Å

25671

7t3u

EMDB-25671, PDB-7t3u:
IP3, ATP, and Ca2+ bound type 3 IP3 receptor in the inactive state
Method: EM (single particle) / Resolution: 3.7 Å

Chemicals

ChemComp-ZN:
Unknown entry

ChemComp-I3P:
D-MYO-INOSITOL-1,4,5-TRIPHOSPHATE

ChemComp-ATP:
ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying molecule*YM

ChemComp-CA:
Unknown entry

Source
  • homo sapiens (human)
KeywordsMETAL TRANSPORT / IP3 receptor / calcium signaling

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