The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
The structural basis of agonist-induced activation in constitutively active rhodopsin
Open accessAbstract
G-protein-coupled receptors (GPCRs) comprise the largest family of membrane proteins in the human genome and mediate cellular responses to an extensive array of hormones, neurotransmitters and sensory stimuli. Although some crystal structures have been determined for GPCRs, most are for modified forms, showing little basal activity, and are bound to inverse agonists or antagonists. Consequently, these structures correspond to receptors in their inactive states. The visual pigment rhodopsin is the only GPCR for which structures exist that are thought to be in the active state. However, these structures are for the apoprotein, or opsin, form that does not contain the agonist all-trans retinal. Here we present a crystal structure at a resolution of 3 Å for the constitutively active rhodopsin mutant Glu 113 Gln in complex with a peptide derived from the carboxy terminus of the α-subunit of the G protein transducin. The protein is in an active conformation that retains retinal in the binding pocket after photoactivation. Comparison with the structure of ground-state rhodopsin suggests how translocation of the retinal β-ionone ring leads to a rotation of transmembrane helix 6, which is the critical conformational change on activation. A key feature of this conformational change is a reorganization of water-mediated hydrogen-bond networks between the retinal-binding pocket and three of the most conserved GPCR sequence motifs. We thus show how an agonist ligand can activate its GPCR.
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
Coot : model-building tools for molecular graphics
Emsley, P., & Cowtan, K. (2004) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444904019158 · Cited by 30,571
Crystal Structure of Rhodopsin: A G Protein-Coupled Receptor
Palczewski, K., Kumasaka, T., Hori, T., Behnke, C. A., Motoshima, H., Fox, B. A., Trong, I. L., Teller, D. C., Okada, T., Stenkamp, R. E., et al. (2000) · Science · doi:10.1126/science.289.5480.739 · Cited by 5,637
Crystal structure of opsin in its G-protein-interacting conformation
Scheerer, P., Park, J. H., Hildebrand, P. W., Kim, Y. J., Krauß, N., Choe, H.-W., Hofmann, K. P., & Ernst, O. P. (2008) · Nature · doi:10.1038/nature07330 · Cited by 1,059
A G protein-coupled receptor at work: the rhodopsin model
Hofmann, K. P., Scheerer, P., Hildebrand, P. W., Choe, H.-W., Park, J. H., Heck, M., & Ernst, O. P. (2009) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2009.07.005 · Cited by 376
Cited by
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
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
Harnessing protein folding neural networks for peptide–protein docking
Tsaban, T., Varga, J. K., Avraham, O., Ben-Aharon, Z., Khramushin, A., & Schueler-Furman, O. (2022) · Nature Communications · doi:10.1038/s41467-021-27838-9 · Cited by 1,205
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
Muscarinic acetylcholine receptors: novel opportunities for drug development
Kruse, A. C., Kobilka, B. K., Gautam, D., Sexton, P. M., Christopoulos, A., & Wess, J. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4295 · Cited by 437
Functions, Therapeutic Applications, and Synthesis of Retinoids and Carotenoids
Álvarez, R., Vaz, B., Gronemeyer, H., & de Lera, Á. R. (2014) · Chemical Reviews · doi:10.1021/cr400126u · Cited by 260
Nanobody stabilization of G protein-coupled receptor conformational states
Steyaert, J., & Kobilka, B. K. (2011) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2011.06.011 · Cited by 234
Labeling and Single-Molecule Methods To Monitor G Protein-Coupled Receptor Dynamics
Tian, H., Fürstenberg, A., & Huber, T. (2017) · Chemical Reviews · doi:10.1021/acs.chemrev.6b00084 · Cited by 114
Preininger, A. M., Meiler, J., & Hamm, H. E. (2013) · Journal of Molecular Biology · doi:10.1016/j.jmb.2013.04.011 · Cited by 104
Orban, T., Jastrzebska, B., Gupta, S., Wang, B., Miyagi, M., Chance, M. R., & Palczewski, K. (2012) · Structure · doi:10.1016/j.str.2012.03.017 · Cited by 67
“…et al., 2007; Nakamichi and Okada, 2006a, 2006b,2007; Okada, 2004; Okada et al., 2004; Palczewski et al., 2000; Salom et al., 2006a, 2006b; Scheerer et al., 2008; Standfuss et al., 2007, 2011; Stenkamp, 2008; Teller et al., 826 Structure 20, 826–840, May 9, 2012 ª2012 Elsevier Ltd All rights 2001).”
Rhodopsin–transducin heteropentamer: Three-dimensional structure and biochemical characterization
Jastrzebska, B., Ringler, P., Lodowski, D. T., Moiseenkova-Bell, V., Golczak, M., Müller, S. A., Palczewski, K., & Engel, A. (2011) · Journal of Structural Biology · doi:10.1016/j.jsb.2011.08.016 · Cited by 57
“…been solved (Salom et al., 2006), the interaction site between Rho and the Gt C-terminus structurally defined (Choe et al., 2011; Scheerer et al., 2008; Standfuss et al., 2011), and the Gta activation by Rho⁄ characterized by site-directed spin labeling and spectroscopy (Van Eps et al., 2011).”
From Atomic Structures to Neuronal Functions of G Protein–Coupled Receptors
Palczewski, K., & Orban, T. (2013) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-062012-170313 · Cited by 44
“Two different constitutively active mutants of rhodopsin (E113Q and M257Y) with a bound C-terminal fragment of a G protein α-subunit were used to trap the activated state of rhodopsin with the agonist all-trans-retinal present in the native-binding pocket (Deupi et al. 2012, Standfuss et al. 2011).”
MethodThe rhodopsin-transducin complex houses two distinct rhodopsin molecules
Jastrzebska, B., Ringler, P., Palczewski, K., & Engel, A. (2013) · Journal of Structural Biology · doi:10.1016/j.jsb.2013.02.014 · Cited by 42
Paoli, M., Münch, D., Haase, A., Skoulakis, E., Turin, L., & Galizia, C. G. (2017) · eneuro · doi:10.1523/eneuro.0070-17.2017 · Cited by 27
Leemann, S., & Kleinlogel, S. (2023) · doi:10.1101/2023.01.27.525823 · Cited by 2
Metadata
- Authors
- Standfuss, J., Edwards, P. C., D’Antona, A., Fransen, M., Xie, G., Oprian, D. D., & Schertler, G. F. X.
- Venue
- Nature
- Published
- 2011-03
- Volume
- 471
- Issue
- 7340
- Pages
- 656-660
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2052091241
- Cited by
- 476
- References
- 4
- FWCI
- 26.33
- 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
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.
