5X9Z

Crystal structure of inositol 1,4,5-trisphosphate receptor large cytosolic domain

Summary for 5X9Z

• Entry DOI: 10.2210/pdb5x9z/pdb
• Related: 5XA0 5XA1
• Descriptor: Inositol 1,4,5-trisphosphate receptor type 1 (1 entity in total)
• Functional Keywords: receptor channel calcium, metal transport
• Biological source: Mus musculus (Mouse)
• Cellular location: Endoplasmic reticulum membrane ; Multi-pass membrane protein : P11881
• Total number of polymer chains: 2
• Total formula weight: 504754.62

Authors

Hamada, K.,Miyatake, H.,Terauchi, A.,Mikoshiba, K. (deposition date: 2017-03-10, release date: 2017-04-19, Last modification date: 2023-11-22)

Primary citation

Hamada, K.,Miyatake, H.,Terauchi, A.,Mikoshiba, K.
IP3-mediated gating mechanism of the IP3 receptor revealed by mutagenesis and X-ray crystallography
Proc. Natl. Acad. Sci. U.S.A., 114:4661-4666, 2017

PubMed Abstract: The inositol 1,4,5-trisphosphate (IP) receptor (IPR) is an IP-gated ion channel that releases calcium ions (Ca) from the endoplasmic reticulum. The IP-binding sites in the large cytosolic domain are distant from the Ca conducting pore, and the allosteric mechanism of how IP opens the Ca channel remains elusive. Here, we identify a long-range gating mechanism uncovered by channel mutagenesis and X-ray crystallography of the large cytosolic domain of mouse type 1 IPR in the absence and presence of IP Analyses of two distinct space group crystals uncovered an IP-dependent global translocation of the curvature α-helical domain interfacing with the cytosolic and channel domains. Mutagenesis of the IPR channel revealed an essential role of a leaflet structure in the α-helical domain. These results suggest that the curvature α-helical domain relays IP-controlled global conformational dynamics to the channel through the leaflet, conferring long-range allosteric coupling from IP binding to the Ca channel.

PubMed: 28416699
DOI: 10.1073/pnas.1701420114

Experimental method

X-RAY DIFFRACTION (7.311 Å)