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1.A.7.1.12
P2X7 purinoceptor of 595 aas and 2 TMSs. All residues that are conserved among the P2X receptor subtypes respond to alanine mutagenesis with an inhibition (Y51, Q52, and G323) or a significant decrease (K49, G326, K327, and F328) of 2',3'-O-(benzoyl-4-benzoyl)-ATP (BzATP)-induced current and permeability to ethidium bromide, while the nonconserved residue (F322), which is also present in P2X4 receptors, responds with a 10-fold higher sensitivity to BzATP, much slower deactivation kinetics, and a higher propensity to form the large dye-permeable pore. Rupert et al. 2020 examined the membrane expression of conserved mutants and found that Y51, Q52, G323, and F328 play a role in the trafficking of the receptor to the plasma membrane, while K49 controls receptor responsiveness to agonists. The K49R, F322Y, F322W, and F322L mutants reversed the receptor function, indicating that positively charged and large hydrophobic residues are important at positions 49 and 322, respectively. Thus, clusters of conserved residues above the transmembrane domain 1 (K49-Y51-Q52) and transmembrane domain 2 (G326-K327-F328) are important for receptor structure, membrane expression, and channel gating and that the nonconserved residue (F322) at the top of the extracellular vestibule is involved in hydrophobic inter-subunit interaction which stabilizes the closed state of the P2X7 receptor channel (Rupert et al. 2020). This protein is 80% identical to the human ortholog (TC# 1.A.7.1.3). The P2X7 receptor in normal and cancer cells, in the perspective of nucleotide signaling, has been reviewed (Matyśniak et al. 2022). N-Methyl-(2S, 4R)-trans-4-hydroxy-L-proline, the major bioactive compound from Sideroxylon obtusifolium, attenuates pilocarpine-induced injury in cultured astrocytes. The improvement of ROS accumulation, VDAC-1 overexpression, and mitochondrial depolarization are possible mechanisms of the NMP protective action on reactive astrocytes (Aquino et al. 2022). The large intracellular C-terminus of the pro-inflammatory P2X7 ion channel receptor (P2X7R) is associated with diverse P2X7R-specific functions. Cryo-EM structures of the closed and ATP-bound open full-length P2X7R identified a membrane-associated anchoring domain, an open-state stabilizing 'cap' domain, and a globular 'ballast domain' containing GTP/GDP and dinuclear Zn2+-binding sites with unknown functions. To investigate protein dynamics during channel activation, Durner et al. 2023 incorporated the environment-sensitive fluorescent unnatural amino acid, L-3-(6-acetylnaphthalen-2-ylamino)-2-aminopropanoic acid (ANAP) into Xenopus laevis oocyte-expressed P2X7Rs and performed voltage clamp fluorometry (VCF). Predicted conformational changes within the extracellular and the transmembrane domains were confirmed. The ballast domain functions fairly independently of the extracellular ATP binding domain and may require activation by additional ligands and/or protein interactions (Durner et al. 2023).  The P2X7 receptor provides a mechanistic biomarker for epilepsy (Engel 2023). Puerarin inhibits NLRP3-caspase-1-GSDMD-mediated pyroptosis via the P2X7 receptor in cardiomyocytes and macrophages (Sun et al. 2023).
 

Accession Number:Q64663
Protein Name:P2X purinoceptor 7
Length:595
Molecular Weight:68392.00
Species:Rattus norvegicus (Rat) [10116]
Number of TMSs:2
Location1 / Topology2 / Orientation3: Cell membrane1 / Multi-pass membrane protein2
Substrate ion, ethidium bromide, dye

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FASTA formatted sequence
1:	MPACCSWNDV FQYETNKVTR IQSVNYGTIK WILHMTVFSY VSFALMSDKL YQRKEPLISS 
61:	VHTKVKGVAE VTENVTEGGV TKLVHGIFDT ADYTLPLQGN SFFVMTNYLK SEGQEQKLCP 
121:	EYPSRGKQCH SDQGCIKGWM DPQSKGIQTG RCIPYDQKRK TCEIFAWCPA EEGKEAPRPA 
181:	LLRSAENFTV LIKNNIDFPG HNYTTRNILP GMNISCTFHK TWNPQCPIFR LGDIFQEIGE 
241:	NFTEVAVQGG IMGIEIYWDC NLDSWSHRCQ PKYSFRRLDD KYTNESLFPG YNFRYAKYYK 
301:	ENGMEKRTLI KAFGVRFDIL VFGTGGKFDI IQLVVYIGST LSYFGLATVC IDLIINTYAS 
361:	TCCRSRVYPS CKCCEPCAVN EYYYRKKCEP IVEPKPTLKY VSFVDEPHIW MVDQQLLGKS 
421:	LQDVKGQEVP RPQTDFLELS RLSLSLHHSP PIPGQPEEMQ LLQIEAVPRS RDSPDWCQCG 
481:	NCLPSQLPEN RRALEELCCR RKPGQCITTS ELFSKIVLSR EALQLLLLYQ EPLLALEGEA 
541:	INSKLRHCAY RSYATWRFVS QDMADFAILP SCCRWKIRKE FPKTQGQYSG FKYPY