Structural highlights
8p1h is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Method: | X-ray diffraction, Resolution 1.95Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Disease
ACHA7_HUMAN 15q13.3 microdeletion syndrome.
Function
E7EX29_HUMAN ACHA7_HUMAN After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane. The channel is blocked by alpha-bungarotoxin.
Publication Abstract from PubMed
Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels composed of five homologous subunits. The homopentameric alpha7-nAChR, abundantly expressed in the brain, is involved in the regulation of the neuronal plasticity and memory and undergoes phosphorylation by protein kinase A (PKA). Here, we extracted native alpha7-nAChR from murine brain, validated its assembly by cryo-EM and showed that phosphorylation by PKA in vitro enables its interaction with the abundant human brain protein 14-3-3zeta. Bioinformatic analysis narrowed the putative 14-3-3-binding site down to the fragment of the intracellular loop (ICL) containing Ser365 (Q(361)RRCSLASVEMS(372)), known to be phosphorylated in vivo. We reconstructed the 14-3-3zeta/ICL peptide complex and determined its structure by X-ray crystallography, which confirmed the Ser365 phosphorylation-dependent canonical recognition of the ICL by 14-3-3. A common mechanism of nAChRs' regulation by ICL phosphorylation and 14-3-3 binding that potentially affects nAChR activity, stoichiometry, and surface expression is suggested.
Crystal structure reveals canonical recognition of the phosphorylated cytoplasmic loop of human alpha7 nicotinic acetylcholine receptor by 14-3-3 protein.,Sluchanko NN, Kapitonova AA, Shulepko MA, Kukushkin ID, Kulbatskii DS, Tugaeva KV, Varfolomeeva LA, Minyaev ME, Boyko KM, Popov VO, Kirpichnikov MP, Lyukmanova EN Biochem Biophys Res Commun. 2023 Sep 28;682:91-96. doi: , 10.1016/j.bbrc.2023.09.086. PMID:37804592[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Sluchanko NN, Kapitonova AA, Shulepko MA, Kukushkin ID, Kulbatskii DS, Tugaeva KV, Varfolomeeva LA, Minyaev ME, Boyko KM, Popov VO, Kirpichnikov MP, Lyukmanova EN. Crystal structure reveals canonical recognition of the phosphorylated cytoplasmic loop of human alpha7 nicotinic acetylcholine receptor by 14-3-3 protein. Biochem Biophys Res Commun. 2023 Sep 28;682:91-96. PMID:37804592 doi:10.1016/j.bbrc.2023.09.086
