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https ://en dot wikipedia dot org /wiki/Protein_Data_Bank

http ://pdb101 dot rcsb dot org/motm/164 == the david goodsell molecule of the month, serotonin receptor ==

Serotonin Receptor

Serotonin receptors control mood, emotion, and many other behaviors, and are targets for many important drugs


Are you feeling happy today? Are you feeling hungry? Do you get migraines? All of these behaviors, and many more, are controlled in part by the neurotransmitter serotonin. Serotonin, a small molecule made from the amino acid tryptophan, was discovered for its role in the constriction of blood vessels. Most of the serotonin in your body is found in the digestive system where it helps to control the motions needed for digestion. However, the most dramatic effects of serotonin are in the brain. Less than one in a million neurons uses serotonin for communication, but these neurons help to control our emotions, moods and thoughts.

Serotonin receptor with an antimigraine drug. The membrane is shown schematically in gray.

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Moody Signals

Serotonin is released from vesicles in nerve cells and picked up by receptors on the target cell surface. There are 15 different forms of these receptors in our bodies, most of which are G protein-coupled receptors like the one shown here from PDB entry 4iar . Serotonin binds to the portion of the receptor on the outside of the cell (shown here at the top of the picture). This induces subtle changes in the shape of the protein and sends a signal to G proteins inside the cell. In some cases, this leads to an excitatory response in the cells, and in other cases it is inhibitory, all depending on the particular receptor and its individual cellular context.

Stopping Serotonin

Many different drugs bind to serotonin receptors and modify the normal signaling process. The structure shown here has the drug ergotamine bound in the site normally occupied by serotonin. Ergotamine activates the receptor and has been used to control the painful swelling of blood vessels that cause migraines. LSD, on the other hand, interferes with serotonin receptors involved in perception, inducing hallucinations and synesthesia. Given the central role of serotonin in the control of many emotional and physiological processes, researchers are searching for new drugs to block serotonin receptors and transporters. The challenge, however, is that the many receptors are very similar, so serotonin-blocking drugs may have deadly side effects. The appetite-suppressing drug Fen-Phen, which had to be recalled, is a perfect example: it blocks the receptor involved in appetite, but also attacks receptors involved in control of heart valves.

Serotonin Transport

Once serotonin has finished its signaling task, it is transported back into the nerve cell by a serotonin transporter protein. This transporter is found in the cell membrane, and transports a sodium ion and a chloride ion along with each molecule of serotonin. A similar transporter is shown here from bacterial cells, from PDB entry 3gwv . Like the serotonin receptor, the serotonin transporter is the target of many drugs used to treat depression. For instance, the structure shown here has fluoxetine (also known as Prozac) blocking the transport tunnel. The serotonin transporter is also one of the targets of drugs of abuse, including amphetamines such as “ecstasy”.

Bacterial leucine transporter with leucine.

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Exploring the Structure

Serotonin Receptors (PDB entries 4iar and 4ib4)

Researchers are trying to make serotonin-mimicking drugs more specific by taking advantage of the portions of serotonin receptors that are different. Two structures of different serotonin receptors with ergotamine, in PDB entries 4iar  and 4ib4 , show one possible approach. Ergotamine is much larger than serotonin, with a portion similar to serotonin (shown in green) that binds deep in the receptor pocket, and the rest binding higher in the pocket. Most of the differences between receptors are found in these more distant portions of the binding site, and may provide new opportunities for designing specific drugs. To look at these structures in more detail, click on the image for an interactive Jmol.

Topics for Further Discussion

  1. You can see the interaction between a G protein-coupled receptor and a G protein in PDB entry 3sn6.
  2. Structures for many other G protein-coupled receptors have been solved, including opsin and adrenergic receptors. You can compare their similar structures, composed of seven alpha helices, using the Compare Structures tool.
  3. The structures of the serotonin receptor, and several other GPCRs, were determined using an engineered protein that has another small protein inserted into the protein chain. Why would this be necessary? What protein was used in the serotonin receptor structures?


  1. 4iar & 4ibr: C. Wang, Y. Jiang, J. Ma, H. Wu, D. Wacker, V. Katritch, G. W. Han, W. Liu, X. P. Huang, E. Vardy, J. D. McCorvy, X. Gao, X. E. Zhou, K. Melcher, C. Zhang, F. Bai, H. Yang, L. Yang, H. Jiang, B. L. Roth, V. Cherezov, R. C. Stevens & H. E. Xu (2013) Structural basis for molecular recognition at serotonin receptors. Science 340, 610-619.
  2. J. G. Hensler (2012) Serotonin. In “Basic Neurochemistry, 8th Edition” Elsevier.
  3. M. Berger, J. A. Gray & B. L. Roth (2009) The expanded biology of serotonin. Annual Review of Medicine 60, 355-366.
  4. 3gwv: Z. Zhou, J. Zhen, N. K. Karpowich, C. J. Law, M. E. A. Reith & D. N. Wang (2009) Antidepressant specificity of serotonin transporter suggested by three LeuT-SSRI structures. Nature Structural & Molecular Biology 16, 652-658.

August 2013, David Goodsell


About Molecule of the Month
The RCSB PDB Molecule of the Month by David S. Goodsell (The Scripps Research Institute and the RCSB PDB) presents short accounts on selected molecules from the Protein Data Bank. Each installment includes an introduction to the structure and function of the molecule, a discussion of the relevance of the molecule to human health and welfare, and suggestions for how visitors might view these structures and access further details. More

___________ October 31, 2019, The library just called and the novel is available for pick-up. First I ought to get a reading light and — I guess I’ll have to check the WalMart for lightbulbs because they’ve gotten so expensive since I’d accidentally knocked a little packet over in 2005, it fell to the floor of maybe a Walgreen’s in Brighton Beach, Brooklyn and this next time I’ve looked they’re nearly seven instead of 2-3 dollars a package anymore so coordinating both a lamp and a lightbulb for it, 40-watt only and then I figure those won’t be that good so I’ll have to try to get those errands done and I don’t even know what I’m doing out on such a cold day nearly, have to get in before the temperature drops tonight into the thirties, shudder shudder for me. I’ll put this in the regular post but thought I’d make the note that “Receptor” is really only for the parts of the novel, 2019 somehow for me to have learned about to manage to read while something’s contemporary still, that I’m only going to skim it for the “good” parts that I’m looking for, about that “milquetoast” accountant-type that sounds maybe like the Edsel Ford type, is why I’m going to try to quickly look into it for the parts about him/Frank Olson -type et al.

About kathyfoshay

I'm all alone with the real end of the world and always looking for assistance and no one's ever contacted me from the hundreds of letters I'd sent while at the big homeless shelter, 2nd and D Streets, NW, as though anyone that tries to contact me gets disappeared, my life used as a LURE-gimmick that goes to how that Armageddon prophecy in that book of Revelation has been being snuck-through, and this is sort of the bottom of the barrel of ideas for trying to find assistance, thinking I could get all my various writings on this in one place that letter-recipients could then look up if they're interested. That means I'd have to see if I can send my emails to here, how to do that. Wordpress said there is a way but it entails that spam would also get the email address. My time for now it up I guess. Working in this sitting position isn't healthy for me but I've always got to be doing something toward trying to get hold of someone to help me. It's like I'm a microcosm of the Earth or the human race and if someone could help me out of this torture then that'd be a start on trying to get the whole Earth out of this. 5/1/17, still all this, etc., same situation. (7/14/18 now....) Now it's 2019.
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