Inositol trisphosphate receptor explained

See also: Ryanodine-Inositol 1,4,5-triphosphate receptor calcium channels.

inositol 1,4,5-trisphosphate receptor, type 1[1]
Caption:Crystal structure of the ligand binding suppressor domain of type 1 inositol 1,4,5-trisphosphate receptor
Hgncid:6180
Symbol:ITPR1
Entrezgene:3708
Omim:147265
Refseq:NM_002222
Uniprot:Q14643
Chromosome:3
Arm:p
Band:26.1
inositol 1,4,5-trisphosphate receptor, type 2
Hgncid:Crystal structure of the ligand binding suppressor domain of type 1 inositol 1,4,5-trisphosphate receptor 6181
Symbol:ITPR2
Entrezgene:3709
Omim:600144
Refseq:NM_002223
Uniprot:Q14571
Chromosome:12
Arm:p
Band:11.23
inositol 1,4,5-trisphosphate receptor, type 3
Caption:Single-particle cryo-EM structure of the IP3-bound resting state.
Hgncid:6182
Symbol:ITPR3
Entrezgene:3710
Omim:147267
Refseq:NM_002224
Uniprot:Q14573
Chromosome:6
Arm:p
Band:21.31

Inositol trisphosphate receptor (InsP3R) is a membrane glycoprotein complex acting as a Ca2+ channel activated by inositol trisphosphate (InsP3). InsP3R is very diverse among organisms, and is necessary for the control of cellular and physiological processes including cell division, cell proliferation, apoptosis, fertilization, development, behavior, learning and memory.[2] Inositol triphosphate receptor represents a dominant second messenger leading to the release of Ca2+ from intracellular store sites. There is strong evidence suggesting that the InsP3R plays an important role in the conversion of external stimuli to intracellular Ca2+ signals characterized by complex patterns relative to both space and time, such as Ca2+ waves and oscillations.[3]

Discovery

The InsP3 receptor was first purified from rat cerebellum by neuroscientists Surachai Supattapone and Solomon Snyder at Johns Hopkins University School of Medicine.[4]

The cDNA of the InsP3 receptor was first cloned in the laboratory of Katsuhiko Mikoshiba. The initial sequencing was reported as an unknown protein enriched in the cerebellum called P400.[5] The large size of this open reading frame indicated a molecular weight similar to the protein purified biochemically, and soon thereafter it was confirmed that the protein p400 was in fact the inositol trisphosphate receptor.[6]

Distribution

The receptor has a broad tissue distribution but is especially abundant in the cerebellum. Most of the InsP3Rs are found integrated into the endoplasmic reticulum.

Structure

Several X-ray crystallographic [7] [8] [9] and electron cryomicroscopic (cryo-EM) [10] [11] [12] [13] [14] [15] [16] structures of IP3Rs from mouse, rat, and human have defined the overall architecture of the channel. The 1.2 MDa C4-symmetric assembly consists of an ER-embedded transmembrane domain (TMD) in a domain-swapped 6 transmembrane (6TM) cation channel fold that is capped by a large cytosolic domain (CD). In this manner, IP3Rs share significant homology with the much larger and distantly-related RyRs.[17] The CD contains all known ligand binding sites, including the IP3 binding site, two Ca2+ binding sites, an adenine nucleotide binding site, and a C2H2 Zn2+ finger fold. A comprehensive Ca2+-dependent conformational landscape has been defined by cryo-EM.[18]

See also

Notes and References

  1. Bosanac I, Yamazaki H, Matsu-Ura T, Michikawa T, Mikoshiba K, Ikura M . Crystal structure of the ligand binding suppressor domain of type 1 inositol 1,4,5-trisphosphate receptor . Molecular Cell . 17 . 2 . 193–203 . January 2005 . 15664189 . 10.1016/j.molcel.2004.11.047 . free .
  2. Bosanac I, Alattia JR, Mal TK, Chan J, Talarico S, Tong FK, Tong KI, Yoshikawa F, Furuichi T, Iwai M, Michikawa T, Mikoshiba K, Ikura M . 6 . Structure of the inositol 1,4,5-trisphosphate receptor binding core in complex with its ligand . Nature . 420 . 6916 . 696–700 . December 2002 . 12442173 . 10.1038/nature01268 . 4422308 . 2002Natur.420..696B .
  3. Yoshida Y, Imai S . Structure and function of inositol 1,4,5-trisphosphate receptor . Japanese Journal of Pharmacology . 74 . 2 . 125–137 . June 1997 . 9243320 . 10.1254/jjp.74.125 . free .
  4. Supattapone S, Worley PF, Baraban JM, Snyder SH . Solubilization, purification, and characterization of an inositol trisphosphate receptor . The Journal of Biological Chemistry . 263 . 3 . 1530–1534 . January 1988 . 2826483 . 10.1016/S0021-9258(19)57336-7 . free .
  5. Furuichi T, Yoshikawa S, Mikoshiba K . Nucleotide sequence of cDNA encoding P400 protein in the mouse cerebellum . Nucleic Acids Research . 17 . 13 . 5385–5386 . July 1989 . 2762133 . 318125 . 10.1093/nar/17.13.5385 .
  6. Furuichi T, Yoshikawa S, Miyawaki A, Wada K, Maeda N, Mikoshiba K . Primary structure and functional expression of the inositol 1,4,5-trisphosphate-binding protein P400 . Nature . 342 . 6245 . 32–38 . November 1989 . 2554142 . 10.1038/342032a0 . 1781700 . 1989Natur.342...32F .
  7. Bosanac I, Alattia JR, Mal TK, Chan J, Talarico S, Tong FK, Tong KI, Yoshikawa F, Furuichi T, Iwai M, Michikawa T, Mikoshiba K, Ikura M . 6 . Structure of the inositol 1,4,5-trisphosphate receptor binding core in complex with its ligand . Nature . 420 . 6916 . 696–700 . December 2002 . 12442173 . 10.1038/nature01268 . 2002Natur.420..696B . 4422308 .
  8. Lin CC, Baek K, Lu Z . Apo and InsP₃-bound crystal structures of the ligand-binding domain of an InsP₃ receptor . Nature Structural & Molecular Biology . 18 . 10 . 1172–1174 . September 2011 . 21892169 . 10.1038/nsmb.2112 . 3242432 .
  9. Seo MD, Velamakanni S, Ishiyama N, Stathopulos PB, Rossi AM, Khan SA, Dale P, Li C, Ames JB, Ikura M, Taylor CW . 6 . Structural and functional conservation of key domains in InsP3 and ryanodine receptors . Nature . 483 . 7387 . 108–112 . January 2012 . 22286060 . 10.1038/nature10751 . 3378505 . 2012Natur.483..108S .
  10. Fan G, Baker ML, Wang Z, Baker MR, Sinyagovskiy PA, Chiu W, Ludtke SJ, Serysheva II . 6 . Gating machinery of InsP3R channels revealed by electron cryomicroscopy . Nature . 527 . 7578 . 336–341 . November 2015 . 26458101 . 10.1038/nature15249 . 4804758 . 2015Natur.527..336F .
  11. Paknejad N, Hite RK . Structural basis for the regulation of inositol trisphosphate receptors by Ca2+ and IP3 . Nature Structural & Molecular Biology . 25 . 8 . 660–668 . August 2018 . 30013099 . 10.1038/s41594-018-0089-6 . 6082148 .
  12. Fan G, Baker MR, Wang Z, Seryshev AB, Ludtke SJ, Baker ML, Serysheva II . Cryo-EM reveals ligand induced allostery underlying InsP3R channel gating . Cell Research . 28 . 12 . 1158–1170 . December 2018 . 30470765 . 10.1038/s41422-018-0108-5 . 6274648 .
  13. Azumaya CM, Linton EA, Risener CJ, Nakagawa T, Karakas E . Cryo-EM structure of human type-3 inositol triphosphate receptor reveals the presence of a self-binding peptide that acts as an antagonist . The Journal of Biological Chemistry . 295 . 6 . 1743–1753 . February 2020 . 31915246 . 10.1074/jbc.RA119.011570 . 7008357 . free .
  14. Baker MR, Fan G, Seryshev AB, Agosto MA, Baker ML, Serysheva II . Cryo-EM structure of type 1 IP3R channel in a lipid bilayer . Communications Biology . 4 . 1 . 625 . May 2021 . 34035440 . 10.1038/s42003-021-02156-4 . 8149723 .
  15. Schmitz EA, Takahashi H, Karakas E . Structural basis for activation and gating of IP3 receptors . Nature Communications . 13 . 1 . 1408 . March 2022 . 35301323 . 10.1038/s41467-022-29073-2 . 8930994 . 2022NatCo..13.1408S .
  16. Fan G, Baker MR, Terry LE, Arige V, Chen M, Seryshev AB, Baker ML, Ludtke SJ, Yule DI, Serysheva II . 6 . Conformational motions and ligand-binding underlying gating and regulation in IP3R channel . Nature Communications . 13 . 1 . 6942 . November 2022 . 36376291 . 10.1038/s41467-022-34574-1 . 9663519 . 2022NatCo..13.6942F .
  17. Woll KA, Van Petegem F . Calcium-release channels: structure and function of IP3 receptors and ryanodine receptors . Physiological Reviews . 102 . 1 . 209–268 . January 2022 . 34280054 . 10.1152/physrev.00033.2020 . 236141016 . free .
  18. Paknejad . Navid . Sapuru . Vinay . Hite . Richard K. . 2023-10-28 . Structural titration reveals Ca2+-dependent conformational landscape of the IP3 receptor . Nature Communications . en . 14 . 1 . 6897 . 10.1038/s41467-023-42707-3 . 2041-1723 . 10613215 . 37898605.

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