The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
Structure and dynamics of the M3 muscarinic acetylcholine receptor
Open accessAbstract
Acetylcholine, the first neurotransmitter to be identified, exerts many of its physiological actions via activation of a family of G-protein-coupled receptors (GPCRs) known as muscarinic acetylcholine receptors (mAChRs). Although the five mAChR subtypes (M1–M5) share a high degree of sequence homology, they show pronounced differences in G-protein coupling preference and the physiological responses they mediate. Unfortunately, despite decades of effort, no therapeutic agents endowed with clear mAChR subtype selectivity have been developed to exploit these differences. We describe here the structure of the Gq/11-coupled M3 mAChR (‘M3 receptor’, from rat) bound to the bronchodilator drug tiotropium and identify the binding mode for this clinically important drug. This structure, together with that of the Gi/o-coupled M2 receptor, offers possibilities for the design of mAChR subtype-selective ligands. Importantly, the M3 receptor structure allows a structural comparison between two members of a mammalian GPCR subfamily displaying different G-protein coupling selectivities. Furthermore, molecular dynamics simulations suggest that tiotropium binds transiently to an allosteric site en route to the binding pocket of both receptors. These simulations offer a structural view of an allosteric binding mode for an orthosteric GPCR ligand and provide additional opportunities for the design of ligands with different affinities or binding kinetics for different mAChR subtypes. Our findings not only offer insights into the structure and function of one of the most important GPCR families, but may also facilitate the design of improved therapeutics targeting these critical receptors.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
VMD: visual molecular dynamics
Humphrey, W., Dalke, A., & Schulten, K. (1996) · Journal of Molecular Graphics · doi:10.1016/0263-7855(96)00018-5 · Cited by 66,952
[20] Processing of X-ray diffraction data collected in oscillation mode
Otwinowski, Z., & Minor, W. (1997) · Methods in Enzymology · doi:10.1016/s0076-6879(97)76066-x · Cited by 33,475
PHENIX : a comprehensive Python-based system for macromolecular structure solution
Adams, P. D., Afonine, P. V., Bunkóczi, G., Chen, V. B., Davis, I. W., Echols, N., Headd, J. J., Hung, L.-W., Kapral, G. J., Grosse-Kunstleve, R. W., et al. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444909052925 · Cited by 23,716
Phaser crystallographic software
McCoy, A. J., Grosse-Kunstleve, R. W., Adams, P. D., Winn, M. D., Storoni, L. C., & Read, R. J. (2007) · Journal of Applied Crystallography · doi:10.1107/s0021889807021206 · Cited by 20,612
Crystal structure of the β2 adrenergic receptor–Gs protein complex
Rasmussen, S. G. F., DeVree, B. T., Zou, Y., Kruse, A. C., Chung, K. Y., Kobilka, T. S., Thian, F. S., Chae, P. S., Pardon, E., Calinski, D., et al. (2011) · Nature · doi:10.1038/nature10361 · Cited by 3,009
Self-citationMuscarinic acetylcholine receptors: mutant mice provide new insights for drug development
Wess, J., Eglen, R. M., & Gautam, D. (2007) · Nature Reviews Drug Discovery · doi:10.1038/nrd2379 · Cited by 637
Self-citationMillisecond-scale molecular dynamics simulations on Anton
Shaw, D. E., Dror, R. O., Salmon, J. K., Grossman, J. P., Mackenzie, K. M., Bank, J. A., Young, C., Deneroff, M. M., Batson, B., Bowers, K. J., et al. (2009) · Proceedings of the Conference on High Performance Computing Networking, Storage and Analysis · doi:10.1145/1654059.1654099 · Cited by 382
Self-citation
Cited by
The Molecular Basis of G Protein–Coupled Receptor Activation
Weis, W. I., & Kobilka, B. K. (2018) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060614-033910 · Cited by 1,227
Self-citationActivation and allosteric modulation of a muscarinic acetylcholine receptor
Kruse, A. C., Ring, A. M., Manglik, A., Hu, J., Hu, K., Eitel, K., Hübner, H., Pardon, E., Valant, C., Sexton, P. M., et al. (2013) · Nature · doi:10.1038/nature12735 · Cited by 893
Self-citationGPCR Dynamics: Structures in Motion
Latorraca, N. R., Venkatakrishnan, A. J., & Dror, R. O. (2017) · Chemical Reviews · doi:10.1021/acs.chemrev.6b00177 · Cited by 835
Self-citationG protein-coupled receptors: structure- and function-based drug discovery
Yang, D., Zhou, Q., Labroska, V., Qin, S., Darbalaei, S., Wu, Y., Yuliantie, E., Xie, L., Tao, H., Cheng, J., et al. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00435-w · Cited by 632
Emerging paradigms in GPCR allostery: implications for drug discovery
Wootten, D., Christopoulos, A., & Sexton, P. M. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd4052 · Cited by 498
Metadata
- Authors
- Kruse, A. C., Hu, J., Pan, A. C., Arlow, D. H., Rosenbaum, D. M., Rosemond, E., Green, H. F., Liu, T., Chae, P. S., Dror, R. O., Shaw, D. E., Weis, W. I., Wess, J., & Kobilka, B. K.
- Venue
- Nature
- Published
- 2012-02
- Volume
- 482
- Issue
- 7386
- Pages
- 552-556
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2047144511
- Cited by
- 811
- References
- 7
- FWCI
- 39.96
- Type
- journal article
- Language
- en
- Open access
- green
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Structure and dynamics of the M3 muscarinic acetylcholine receptor. https://app.cochat.ai/papers/10.1038/nature10867
- The paper
- Kruse, A. C., Hu, J., Pan, A. C., Arlow, D. H., Rosenbaum, D. M., Rosemond, E., Green, H. F., Liu, T., Chae, P. S., Dror, R. O., Shaw, D. E., Weis, W. I., Wess, J., & Kobilka, B. K. (2012). Structure and dynamics of the M3 muscarinic acetylcholine receptor. Nature. https://doi.org/10.1038/nature10867
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
