| Title |
Crystal Structure of an LSD-Bound Human Serotonin Receptor
|
|---|---|
| Published in |
Cell, January 2017
|
| DOI | 10.1016/j.cell.2016.12.033 |
| Pubmed ID | |
| Authors |
Daniel Wacker, Sheng Wang, John D. McCorvy, Robin M. Betz, A.J. Venkatakrishnan, Anat Levit, Katherine Lansu, Zachary L. Schools, Tao Che, David E. Nichols, Brian K. Shoichet, Ron O. Dror, Bryan L. Roth |
| Abstract |
The prototypical hallucinogen LSD acts via serotonin receptors, and here we describe the crystal structure of LSD in complex with the human serotonin receptor 5-HT2B. The complex reveals conformational rearrangements to accommodate LSD, providing a structural explanation for the conformational selectivity of LSD's key diethylamide moiety. LSD dissociates exceptionally slow from both 5-HT2BR and 5-HT2AR-a major target for its psychoactivity. Molecular dynamics (MD) simulations suggest that LSD's slow binding kinetics may be due to a "lid" formed by extracellular loop 2 (EL2) at the entrance to the binding pocket. A mutation predicted to increase the mobility of this lid greatly accelerates LSD's binding kinetics and selectively dampens LSD-mediated β-arrestin2 recruitment. This study thus reveals an unexpected binding mode of LSD; illuminates key features of its kinetics, stereochemistry, and signaling; and provides a molecular explanation for LSD's actions at human serotonin receptors. PAPERCLIP. |
X Demographics
The data shown below were collected from the profiles of 312 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 108 | 35% |
| United Kingdom | 14 | 4% |
| Germany | 8 | 3% |
| Canada | 8 | 3% |
| Mexico | 7 | 2% |
| France | 5 | 2% |
| Chile | 3 | <1% |
| Australia | 3 | <1% |
| Spain | 2 | <1% |
| Other | 25 | 8% |
| Unknown | 129 | 41% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 238 | 76% |
| Scientists | 63 | 20% |
| Practitioners (doctors, other healthcare professionals) | 8 | 3% |
| Science communicators (journalists, bloggers, editors) | 3 | <1% |
Mendeley readers
The data shown below were compiled from readership statistics for 877 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 7 | <1% |
| United Kingdom | 3 | <1% |
| Mexico | 2 | <1% |
| Austria | 1 | <1% |
| Netherlands | 1 | <1% |
| Canada | 1 | <1% |
| Singapore | 1 | <1% |
| Australia | 1 | <1% |
| China | 1 | <1% |
| Other | 3 | <1% |
| Unknown | 856 | 98% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 207 | 24% |
| Researcher | 128 | 15% |
| Student > Ph. D. Student | 120 | 14% |
| Student > Master | 85 | 10% |
| Student > Doctoral Student | 44 | 5% |
| Other | 107 | 12% |
| Unknown | 186 | 21% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 170 | 19% |
| Chemistry | 105 | 12% |
| Pharmacology, Toxicology and Pharmaceutical Science | 96 | 11% |
| Agricultural and Biological Sciences | 91 | 10% |
| Neuroscience | 77 | 9% |
| Other | 135 | 15% |
| Unknown | 203 | 23% |
Attention Score in Context
This research output has an Altmetric Attention Score of 865. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 09 April 2024.
All research outputs
#21,091
of 25,789,020 outputs
Outputs from Cell
#156
of 17,277 outputs
Outputs of similar age
#397
of 424,171 outputs
Outputs of similar age from Cell
#6
of 142 outputs
Altmetric has tracked 25,789,020 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 99th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 17,277 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 59.7. This one has done particularly well, scoring higher than 99% of its peers.
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We're also able to compare this research output to 142 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 95% of its contemporaries.