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- Title
Cryo-EM structure of 5-HT<sub>3A</sub> receptor in its resting conformation.
- Authors
Basak, Sandip; Gicheru, Yvonne; Samanta, Amrita; Molugu, Sudheer Kumar; Wei Huang; la de Fuente, Maria; Hughes, Taylor; Taylor, Derek J.; Nieman, Marvin T.; Moiseenkova-Bell, Vera; Chakrapani, Sudha
- Abstract
Serotonin receptors (5-HT3AR) directly regulate gut movement, and drugs that inhibit 5-HT3AR function are used to control emetic reflexes associated with gastrointestinal pathologies and cancer therapies. The 5-HT3AR function involves a finely tuned orchestration of three domain movements that include the ligand-binding domain, the pore domain, and the intracellular domain. Here, we present the structure from the full-length 5-HT3AR channel in the apo-state determined by single-particle cryo-electron microscopy at a nominal resolution of 4.3 Å. In this conformation, the ligand-binding domain adopts a conformation reminiscent of the unliganded state with the pore domain captured in a closed conformation. In comparison to the 5-HT3AR crystal structure, the full-length channel in the apo-conformation adopts a more expanded conformation of all the three domains with a characteristic twist that is implicated in gating.
- Subjects
SEROTONIN receptors; GASTROINTESTINAL cancer; CRYSTAL structure; CANCER treatment; LIGANDS (Biochemistry); ELECTRON microscopy
- Publication
Nature Communications, 2018, Vol 9, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-018-02997-4