Related ArticlesNMR structures of the human ?7 nAChR transmembrane domain and associated anesthetic binding sites.
Biochim Biophys Acta. 2013 Dec 30;
Authors: Bondarenko V, Mowrey DD, Tillman TS, Seyoum E, Xu Y, Tang P
Abstract
The ?7 nicotinic acetylcholine receptor (nAChR), assembled as homomeric pentameric ligand-gated ion channels, is one of the most abundant nAChR subtypes in the brain. Despite its importance in memory, learning and cognition, no structure has been determined for the ?7 nAChR TM domain, a target for allosteric modulators. Using solution state NMR, we determined the structure of the human ?7 nAChR TM domain (PDB ID: 2MAW) and demonstrated that the ?7 TM domain formed functional channels in Xenopus oocytes. We identified the associated binding sites for the anesthetics halothane and ketamine; the former cannot sensitively inhibit ?7 function, but latter can. The ?7 TM domain folds into the expected four-helical bundle motif, but the intra-subunit cavity at the extracellular end of the ?7 TM domain is smaller than the equivalent cavity in the ?4?2 nAChRs (PDB IDs: 2LLY; 2LM2). Neither drug binds to the extracellular end of the ?7 TM domain, but two halothane molecules or one ketamine molecule bind to the intracellular end of the ?7 TM domain. Halothane and ketamine binding sites are partially overlapped. Ketamine, but not halothane, perturbed the ?7 channel-gate residue L9'. Furthermore, halothane did not induce profound dynamics changes in the ?7 channel as observed in ?4?2. The study offers a novel high-resolution structure for the human ?7 nAChR TM domain that is invaluable for developing ?7-specific therapeutics. It also provides evidence to support the hypothesis: only when anesthetic binding perturbs the channel pore or alters the channel motion, can binding generate functional consequences.
PMID: 24384062 [PubMed - as supplied by publisher]
[NMR paper] Mapping Functional Interaction Sites of Human Prune C-Terminal Domain by NMR Spectroscopy in Human Cell Lysates.
Mapping Functional Interaction Sites of Human Prune C-Terminal Domain by NMR Spectroscopy in Human Cell Lysates.
Mapping Functional Interaction Sites of Human Prune C-Terminal Domain by NMR Spectroscopy in Human Cell Lysates.
Chemistry. 2013 Aug 12;
Authors: Diana D, Smaldone G, De Antonellis P, Pirone L, Carotenuto M, Alonzi A, Di Gaetano S, Zollo M, Pedone EM, Fattorusso R
Abstract
Get well prune: The C-terminal third domain of h-prune is largely unfolded and involved in relevant protein-protein interactions, particularly with...
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[NMR paper] NMR structures of the transmembrane domains of the ?4?2 nAChR.
NMR structures of the transmembrane domains of the ?4?2 nAChR.
http://www.bionmr.com//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif Related Articles NMR structures of the transmembrane domains of the ?4?2 nAChR.
Biochim Biophys Acta. 2012 May;1818(5):1261-8
Authors: Bondarenko V, Mowrey D, Tillman T, Cui T, Liu LT, Xu Y, Tang P
Abstract
The ?4?2 nicotinic acetylcholine receptor (nAChR) is the predominant heteromeric subtype of nAChRs in the brain, which has been implicated in numerous...
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04-27-2013 01:56 PM
Unravelling the Conformational Plasticity of the Extracellular Domain of a Prokaryotic nAChR Homologue in Solution by NMR
Unravelling the Conformational Plasticity of the Extracellular Domain of a Prokaryotic nAChR Homologue in Solution by NMR
http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/bichaw/0/bichaw.ahead-of-print/bi201223u/aop/images/medium/bi-2011-01223u_0002.gif
Biochemistry
DOI: 10.1021/bi201223u
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Expression, purification, and reconstitution of the transmembrane domain of the human amyloid precursor protein for NMR studies.
Expression, purification, and reconstitution of the transmembrane domain of the human amyloid precursor protein for NMR studies.
Expression, purification, and reconstitution of the transmembrane domain of the human amyloid precursor protein for NMR studies.
Protein Expr Purif. 2011 Aug 31;
Authors: Chen W, Gamache E, Richardson D, Du Z, Wang C
Abstract
Alzheimer's disease (AD) is the most common type of dementia in elderly people. Senile plaques, a pathologic hallmark of AD, are composed of amyloid ? peptide (A?). A? aggregation produces...
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09-13-2011 08:27 PM
Bacterial expression, purification, and model membrane reconstitution of the transmembrane and cytoplasmic domains of the human APP binding protein LR11/SorLA for NMR studies.
Bacterial expression, purification, and model membrane reconstitution of the transmembrane and cytoplasmic domains of the human APP binding protein LR11/SorLA for NMR studies.
Bacterial expression, purification, and model membrane reconstitution of the transmembrane and cytoplasmic domains of the human APP binding protein LR11/SorLA for NMR studies.
Protein Expr Purif. 2011 Feb 11;
Authors: Wang X, Gill Jr RL, Zhu Q, Tian F
LR11 (SorLA) is a recently identified neuronal protein that interacts with amyloid precursor protein (APP), a central player...
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02-16-2011 07:40 PM
[NMR paper] Identification of Li(+) binding sites and the effect of Li(+) treatment on phospholipid composition in human neuroblastoma cells: a (7)Li and (31)P NMR study.
Identification of Li(+) binding sites and the effect of Li(+) treatment on phospholipid composition in human neuroblastoma cells: a (7)Li and (31)P NMR study.
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Biochim Biophys Acta. 2005 Sep 25;1741(3):339-49
Authors: Layden BT, Abukhdeir AM, Malarkey C, Oriti LA, Salah W, Stigler C, Geraldes CF, Mota de Freitas D
Li(+) binding in subcellular fractions of human...
[NMR paper] Application of the 19F NMR technique to observe binding of the general anesthetic hal
Application of the 19F NMR technique to observe binding of the general anesthetic halothane to human serum albumin.
Related Articles Application of the 19F NMR technique to observe binding of the general anesthetic halothane to human serum albumin.
Anal Sci. 2004 Oct;20(10):1475-7
Authors: Shikii K, Sakurai S, Utsumi H, Seki H, Tashiro M
19F NMR techniques were employed to characterize the binding property of the widely used general anesthetic halothane with human serum albumin (HSA). It was found that 19F(1H) NOE and 2D 1H-19F HOESY...
NMR structures of the human ?7 nAChR transmembrane domain and associated anesthetic binding sites.
Linear Mode
