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1.A.9.1.7
The alpha7 (α-7) nicotinic acetylcholine receptor of 502 aas is encoded by the CHRNA7 gene.  Acetylcholine binding induces conformational changes that result in open channel formation; opening is blocked by α-bungarotoxin.  The protein is a homopentamer.  It interacts with RIC3 for proper folding and assembly. The nAChR, but not the glycine receptor, GlyR, exhibits hydrophobic gating (Ivanov et al. 2007). Low resolution NMR structures with associated anesthetics have been reported (Bondarenko et al. 2013).  Allosteric modulators exhibit up to 5 distinct pharmacological effects (Gill-Thind et al. 2015).  Based on pore hydration and size, a high resolution structure for the channel in the open conformation has been proposed (Chiodo et al. 2015). Agonists reduce dyskinesias in both early- and later-stage Parkinson's disease (Zhang et al. 2015). Monoterpenes inhibit the alpha7 receptor in the order: carveol > thymoquinone > carvacrol > menthone > thymol > limonene > eugenole > pulegone = carvone = vanilin. Among the monoterpenes, carveol showed the highest potency (Lozon et al. 2016). A revised structural model has been proposed (Newcombe et al. 2017). In humans, exons 5-10 in CHRNA7 are duplicated and fused to the FAM7A genetic element, giving rise to the hybrid gene CHRFAM7A. Its product, dupalpha7, is a truncated subunit lacking part of the N-terminal extracellular ligand-binding domain and is associated with neurological disorders, including schizophrenia, and immunomodulation (Lasala et al. 2018). alpha7 and dupalpha7 subunits co-assemble into functional heteromeric receptors, that at least two alpha7 subunits are required for channel opening, and that dupalpha7's presence in the pentameric arrangement does not affect the duration of the potentiated events. Using an alpha7 subunit mutant, activation of (alpha7)2(dupalpha7)3 receptors occurs through ACh binding at the alpha7/alpha7 interfacial binding site (Lasala et al. 2018).

Accession Number:P36544
Protein Name:Neuronal acetylcholine receptor subunit alpha-7
Length:502
Molecular Weight:56449.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:4
Location1 / Topology2 / Orientation3: Cell junction1 / Multi-pass membrane protein2
Substrate inorganic cations

Cross database links:

Genevestigator: P36544
eggNOG: prNOG09312
OMIM: 118511  gene+phenotype
Structure:
2MAW   5AFH   5AFJ   5AFK   5AFL   5AFM   5AFN     

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  • 2° Structure (Network Protein Sequence Analysis)

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FASTA formatted sequence
1:	MRCSPGGVWL ALAASLLHVS LQGEFQRKLY KELVKNYNPL ERPVANDSQP LTVYFSLSLL 
61:	QIMDVDEKNQ VLTTNIWLQM SWTDHYLQWN VSEYPGVKTV RFPDGQIWKP DILLYNSADE 
121:	RFDATFHTNV LVNSSGHCQY LPPGIFKSSC YIDVRWFPFD VQHCKLKFGS WSYGGWSLDL 
181:	QMQEADISGY IPNGEWDLVG IPGKRSERFY ECCKEPYPDV TFTVTMRRRT LYYGLNLLIP 
241:	CVLISALALL VFLLPADSGE KISLGITVLL SLTVFMLLVA EIMPATSDSV PLIAQYFAST 
301:	MIIVGLSVVV TVIVLQYHHH DPDGGKMPKW TRVILLNWCA WFLRMKRPGE DKVRPACQHK 
361:	QRRCSLASVE MSAVAPPPAS NGNLLYIGFR GLDGVHCVPT PDSGVVCGRM ACSPTHDEHL 
421:	LHGGQPPEGD PDLAKILEEV RYIANRFRCQ DESEAVCSEW KFAACVVDRL CLMAFSVFTI 
481:	ICTIGILMSA PNFVEAVSKD FA