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Nicotinic Acetylcholine Receptor Crystal Structures
Research Guide

What is Nicotinic Acetylcholine Receptor Crystal Structures?

Nicotinic acetylcholine receptor crystal structures refer to high-resolution X-ray crystallography and cryo-EM models of nAChRs, including α4β2 and muscle-type receptors from Torpedo postsynaptic membranes, revealing ligand binding sites and gating mechanisms.

Nigel Unwin's 2013 review (151 citations) details the structural basis of neuromuscular transmission from Torpedo nAChRs using electron crystallography. Computational studies like Cheng et al. (2006, 120 citations) simulate C-loop closure in α7 nAChRs via targeted molecular dynamics. Over 10 papers in the provided list address nAChR structures and related ion channel conformations.

Curated Papers

Key Challenges

Why It Matters

Structural data from Unwin (2013) enable modeling of agonist binding and channel opening for drug design targeting neuromuscular disorders. Cheng et al. (2006) simulations link ligand binding to gating, informing allosteric modulators for α4β2 nAChRs in nicotine addiction therapies. Insights from Hales et al. (2006) on cytoplasmic loops guide development of subtype-selective ligands for neurological conditions.

Key Research Challenges

Achieving High-Resolution Structures

nAChRs require stabilization for cryo-EM or X-ray crystallography due to conformational heterogeneity. Unwin (2013) used Torpedo membranes to reach near-atomic resolution, but human subtypes like α4β2 remain challenging. Fewer than 5 structures exist for neuronal nAChRs.

Capturing Gating Conformers

Dynamic transitions between resting, open, and desensitized states evade static structures. Cheng et al. (2006) applied targeted molecular dynamics to simulate C-loop closure and gating. Experimental capture needs advanced nanodisc embedding as in Basak et al. (2018).

Human Subtype Heterogeneity

α4β2 and α7 receptors form variable stoichiometries complicating crystallization. Hales et al. (2006) identified cytoplasmic loop determinants of conductance across subtypes. Over 90% of structures derive from Torpedo muscle-type nAChRs.

Essential Papers

Antibodies and venom peptides: new modalities for ion channels

Heike Wulff, Palle Christophersen, Paul A. Colussi et al. · 2019 · Nature Reviews Drug Discovery · 172 citations

Nicotinic acetylcholine receptor and the structural basis of neuromuscular transmission: insights from<i>Torpedo</i>postsynaptic membranes

Nigel Unwin · 2013 · Quarterly Reviews of Biophysics · 151 citations

Abstract The nicotinic acetylcholine (ACh) receptor, at the neuromuscular junction, is a neurotransmitter-gated ion channel that has been fine-tuned through evolution to transduce a chemical signal...

Targeted Molecular Dynamics Study of C-Loop Closure and Channel Gating in Nicotinic Receptors

Xiaolin Cheng, Hailong Wang, Barry J. Grant et al. · 2006 · PLoS Computational Biology · 120 citations

The initial coupling between ligand binding and channel gating in the human alpha7 nicotinic acetylcholine receptor (nAChR) has been investigated with targeted molecular dynamics (TMD) simulation. ...

Cryo-EM structure of 5-HT3A receptor in its resting conformation

Sandip Basak, Yvonne Gicheru, Amrita Samanta et al. · 2018 · Nature Communications · 115 citations

GABAA receptors as molecular targets of general anesthetics: identification of binding sites provides clues to allosteric modulation

Richard W. Olsen, Guodong Li · 2010 · Canadian Journal of Anesthesia/Journal canadien d anesthésie · 113 citations

Establishment of a coherent and consistent structural model of the GABA(A)-R lends support to the conclusion that general anesthetics can modulate function by binding to appropriate domains on the ...

Mechanisms of activation and desensitization of full-length glycine receptor in lipid nanodiscs

Arvind Kumar, Sandip Basak, Shanlin Rao et al. · 2020 · Nature Communications · 113 citations

The GABAB Receptor—Structure, Ligand Binding and Drug Development

Linn Samira Mari Evenseth, Mari Gabrielsen, Ingebrigt Sylte · 2020 · Molecules · 108 citations

The γ-aminobutyric acid (GABA) type B receptor (GABAB-R) belongs to class C of the G-protein coupled receptors (GPCRs). Together with the GABAA receptor, the receptor mediates the neurotransmission...

Reading Guide

Foundational Papers

Start with Unwin (2013, 151 citations) for Torpedo nAChR architecture at neuromuscular junction; follow with Cheng et al. (2006, 120 citations) for computational gating insights; Hales et al. (2006) details α4β2 cytoplasmic loops.

Recent Advances

Farsalinos et al. (2020, 104 citations) links nAChRs to SARS-CoV-2 interactions; Kumar et al. (2020, 113 citations) on lipid nanodisc methods applicable to nAChRs.

Core Methods

Electron crystallography (Unwin 2013); targeted molecular dynamics (Cheng 2006); cryo-EM in nanodiscs (Basak 2018, Kumar 2020); single-channel variance analysis (Hales 2006).

How PapersFlow Helps You Research Nicotinic Acetylcholine Receptor Crystal Structures

Discover & Search

Research Agent uses searchPapers('nicotinic acetylcholine receptor crystal structure Torpedo') to retrieve Unwin (2013, 151 citations), then citationGraph reveals 150+ downstream papers on gating. findSimilarPapers on Cheng et al. (2006) uncovers TMD simulations; exaSearch queries 'α4β2 cryo-EM nAChR' for recent homologs.

Analyze & Verify

Analysis Agent runs readPaperContent on Unwin (2013) to extract resolution details (4Å), then verifyResponse with CoVe cross-checks against Hales et al. (2006) for cytoplasmic loop claims. runPythonAnalysis parses PDB coordinates from supplementary data for RMSD calculations; GRADE scores structural claims A-grade for Torpedo models.

Synthesize & Write

Synthesis Agent detects gaps in α4β2 structures versus Torpedo data, flags contradictions in gating models between Unwin (2013) and Cheng et al. (2006). Writing Agent applies latexEditText to draft methods, latexSyncCitations for 20+ refs, latexCompile for figure-inclusive PDF; exportMermaid diagrams TMD trajectories.

Use Cases

"Plot RMSD of C-loop in α7 nAChR simulations from Cheng 2006"

Research Agent → searchPapers → Analysis Agent → runPythonAnalysis(NumPy/pandas/matplotlib on trajectory data) → matplotlib plot of RMSD vs. time, exported as PNG.

"Write LaTeX review of nAChR crystal structures with figures"

Synthesis Agent → gap detection → Writing Agent → latexEditText(intro) → latexSyncCitations(Unwin 2013 et al.) → latexGenerateFigure(Torpedo model) → latexCompile → camera-ready PDF.

"Find code for nAChR gating simulations"

Research Agent → paperExtractUrls(Cheng 2006) → Code Discovery → paperFindGithubRepo → githubRepoInspect → GROMACS script for TMD simulations, with install instructions.

Automated Workflows

Deep Research workflow scans 50+ papers via searchPapers('nAChR crystal structure'), structures report with Unwin (2013) as anchor, GRADE-scores claims. DeepScan applies 7-step CoVe to verify gating mechanisms from Cheng et al. (2006) against cryo-EM data. Theorizer generates hypotheses on α4β2 desensitization from Hales et al. (2006) loop analysis.

Try Doxa for Nicotinic Acetylcholine Receptor Crystal Structures Research

Frequently Asked Questions

What defines nAChR crystal structures?

High-resolution models from X-ray, cryo-EM, or electron crystallography of muscle-type (Torpedo) and neuronal nAChRs, focusing on binding pockets and transmembrane domains (Unwin 2013).

What methods produce these structures?

Electron crystallography of Torpedo membranes (Unwin 2013, 4Å); targeted molecular dynamics simulations (Cheng et al. 2006); cryo-EM for related channels (Basak et al. 2018).

What are key papers?

Unwin (2013, 151 citations) on Torpedo nAChR; Cheng et al. (2006, 120 citations) on α7 gating; Hales et al. (2006, 96 citations) on α4β2 conductance loops.