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See also: Ryanodine-Inositol 1,4,5-triphosphate receptor calcium channels
inositol 1,4,5-trisphosphate receptor, type 1 [1]
Crystal structure of the ligand binding suppressor domain of type 1 inositol 1,4,5-trisphosphate receptor
Identifiers
SymbolITPR1
NCBI gene 3708
HGNC 6180
OMIM 147265
RefSeq NM_002222
UniProt Q14643
Other data
Locus Chr. 3 p26.1
Search for
Structures Swiss-model
Domains InterPro
inositol 1,4,5-trisphosphate receptor, type 2
Identifiers
SymbolITPR2
NCBI gene 3709
HGNC structure of the ligand binding suppressor domain of type 1 inositol 1,4,5-trisphosphate receptor 6181 Crystal structure of the ligand binding suppressor domain of type 1 inositol 1,4,5-trisphosphate receptor 6181
OMIM 600144
RefSeq NM_002223
UniProt Q14571
Other data
Locus Chr. 12 p11.23
Search for
Structures Swiss-model
Domains InterPro
inositol 1,4,5-trisphosphate receptor, type 3
Single-particle cryo-EM structure of the IP3-bound resting state.
Identifiers
SymbolITPR3
NCBI gene 3710
HGNC 6182
OMIM 147267
RefSeq NM_002224
UniProt Q14573
Other data
Locus Chr. 6 p21.31
Search for
Structures Swiss-model
Domains InterPro

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 recently been defined by cryo-EM. [18]

See also

References

  1. ^ Bosanac I, Yamazaki H, Matsu-Ura T, Michikawa T, Mikoshiba K, Ikura M (January 2005). "Crystal structure of the ligand binding suppressor domain of type 1 inositol 1,4,5-trisphosphate receptor". Molecular Cell. 17 (2): 193–203. doi: 10.1016/j.molcel.2004.11.047. PMID  15664189.
  2. ^ Bosanac I, Alattia JR, Mal TK, Chan J, Talarico S, Tong FK, et al. (December 2002). "Structure of the inositol 1,4,5-trisphosphate receptor binding core in complex with its ligand". Nature. 420 (6916): 696–700. Bibcode: 2002Natur.420..696B. doi: 10.1038/nature01268. PMID  12442173. S2CID  4422308.
  3. ^ Yoshida Y, Imai S (June 1997). "Structure and function of inositol 1,4,5-trisphosphate receptor". Japanese Journal of Pharmacology. 74 (2): 125–137. doi: 10.1254/jjp.74.125. PMID  9243320.
  4. ^ Supattapone S, Worley PF, Baraban JM, Snyder SH (January 1988). "Solubilization, purification, and characterization of an inositol trisphosphate receptor". The Journal of Biological Chemistry. 263 (3): 1530–1534. doi: 10.1016/S0021-9258(19)57336-7. PMID  2826483.
  5. ^ Furuichi T, Yoshikawa S, Mikoshiba K (July 1989). "Nucleotide sequence of cDNA encoding P400 protein in the mouse cerebellum". Nucleic Acids Research. 17 (13): 5385–5386. doi: 10.1093/nar/17.13.5385. PMC  318125. PMID  2762133.
  6. ^ Furuichi T, Yoshikawa S, Miyawaki A, Wada K, Maeda N, Mikoshiba K (November 1989). "Primary structure and functional expression of the inositol 1,4,5-trisphosphate-binding protein P400". Nature. 342 (6245): 32–38. Bibcode: 1989Natur.342...32F. doi: 10.1038/342032a0. PMID  2554142. S2CID  1781700.
  7. ^ Bosanac I, Alattia JR, Mal TK, Chan J, Talarico S, Tong FK, et al. (December 2002). "Structure of the inositol 1,4,5-trisphosphate receptor binding core in complex with its ligand". Nature. 420 (6916): 696–700. Bibcode: 2002Natur.420..696B. doi: 10.1038/nature01268. PMID  12442173. S2CID  4422308.
  8. ^ Lin CC, Baek K, Lu Z (September 2011). "Apo and InsP₃-bound crystal structures of the ligand-binding domain of an InsP₃ receptor". Nature Structural & Molecular Biology. 18 (10): 1172–1174. doi: 10.1038/nsmb.2112. PMC  3242432. PMID  21892169.
  9. ^ Seo MD, Velamakanni S, Ishiyama N, Stathopulos PB, Rossi AM, Khan SA, et al. (January 2012). "Structural and functional conservation of key domains in InsP3 and ryanodine receptors". Nature. 483 (7387): 108–112. Bibcode: 2012Natur.483..108S. doi: 10.1038/nature10751. PMC  3378505. PMID  22286060.
  10. ^ Fan G, Baker ML, Wang Z, Baker MR, Sinyagovskiy PA, Chiu W, et al. (November 2015). "Gating machinery of InsP3R channels revealed by electron cryomicroscopy". Nature. 527 (7578): 336–341. Bibcode: 2015Natur.527..336F. doi: 10.1038/nature15249. PMC  4804758. PMID  26458101.
  11. ^ Paknejad N, Hite RK (August 2018). "Structural basis for the regulation of inositol trisphosphate receptors by Ca2+ and IP3". Nature Structural & Molecular Biology. 25 (8): 660–668. doi: 10.1038/s41594-018-0089-6. PMC  6082148. PMID  30013099.
  12. ^ Fan G, Baker MR, Wang Z, Seryshev AB, Ludtke SJ, Baker ML, Serysheva II (December 2018). "Cryo-EM reveals ligand induced allostery underlying InsP3R channel gating". Cell Research. 28 (12): 1158–1170. doi: 10.1038/s41422-018-0108-5. PMC  6274648. PMID  30470765.
  13. ^ Azumaya CM, Linton EA, Risener CJ, Nakagawa T, Karakas E (February 2020). "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. doi: 10.1074/jbc.RA119.011570. PMC  7008357. PMID  31915246.
  14. ^ Baker MR, Fan G, Seryshev AB, Agosto MA, Baker ML, Serysheva II (May 2021). "Cryo-EM structure of type 1 IP3R channel in a lipid bilayer". Communications Biology. 4 (1): 625. doi: 10.1038/s42003-021-02156-4. PMC  8149723. PMID  34035440.
  15. ^ Schmitz EA, Takahashi H, Karakas E (March 2022). "Structural basis for activation and gating of IP3 receptors". Nature Communications. 13 (1): 1408. Bibcode: 2022NatCo..13.1408S. doi: 10.1038/s41467-022-29073-2. PMC  8930994. PMID  35301323.
  16. ^ Fan G, Baker MR, Terry LE, Arige V, Chen M, Seryshev AB, et al. (November 2022). "Conformational motions and ligand-binding underlying gating and regulation in IP3R channel". Nature Communications. 13 (1): 6942. Bibcode: 2022NatCo..13.6942F. doi: 10.1038/s41467-022-34574-1. PMC  9663519. PMID  36376291.
  17. ^ Woll KA, Van Petegem F (January 2022). "Calcium-release channels: structure and function of IP3 receptors and ryanodine receptors". Physiological Reviews. 102 (1): 209–268. doi: 10.1152/physrev.00033.2020. PMID  34280054. S2CID  236141016.
  18. ^ Paknejad, Navid; Sapuru, Vinay; Hite, Richard K. (2023-10-28). "Structural titration reveals Ca2+-dependent conformational landscape of the IP3 receptor". Nature Communications. 14 (1): 6897. doi: 10.1038/s41467-023-42707-3. ISSN  2041-1723. PMC  10613215. PMID  37898605.

External links

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