Abstract submission formatting: Font: Arial, size 11

1. Title (150 characters + spaces maximum) 2. Authors (full name), with superscript for affiliation 3. Affiliations (Department, Institution, City, State, Country) 4. Abstract (300 words maximum)

Each section must be separated by a paragraph space. Example:

Structural basis for partial agonism and allosteric modulation of the 5-HT 3A receptor

Kevin C. Felt¹ , Madeleine Stauffer¹ , Leslie Salas-Estrada² , Marta Filizola² , Sudha Chakrapani³

¹Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH, USA, ²Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA, ³Department of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, OH, USA

Type-3 serotonin receptors (5-HT₃Rs) are pentameric ligand gated ion channels that mediate fast synaptic signaling in response to binding of the neurotransmitter serotonin. 5-HT₃Rs play a major role in regulating gut motility, secretion, and visceral perception. Hyperactivity of 5-HT₃Rs underlies pathologies such as chemotherapy-induced nausea and vomiting, irritable bowel syndrome, depression, anxiety, bipolar disorder, and excessive visceral pain, making it an important drug target. Previous research has resulted in the structures of the 5-HT_3ARs in complex with the endogenous agonist serotonin, 5-HT₃R antagonists (setrons), and recently, we have identified the structural basis for partial agonism using compounds with varying efficacies. Here we have extended these studies to explore how allosteric modulators affect the efficacy of different partial agonists. We will present structures generated from cryo-electron microscopy imaging, validation of ligand function by two-electrode voltage clamp in wild type and mutant receptors, and molecular dynamics simulation analysis. Together, these studies reveal mechanisms for the functional differences between orthosteric partial agonists, full agonists, antagonists, as well as allosteric modulators of the 5-HT_3AR.

Poster Printing Directions

Judging Rubric

Poor  1  Fair  2  Average  3  Good  4  Excellent  5 

1. Introduction Was the Intro clear? Was it adequate, but concise, and a background provided?
2. Formulation of Hypothesis Was there clear and significant rationale for the study? Was the hypothesis clear and evident?
3. Results Were there clear, readable, appropriately labeled figures? Were the results clearly presented?
4. Conclusions Do the conclusions follow logically from the data and hypothesis?
5. Questions Did the presenter answer the questions thoughtfully and with clarity?
6. Content and Organization Were the slides legible and informative? Was the order and flow of the presentation easy to follow?
7. Skills of Presenter: Ability to describe the work Did the presenter speak well and clearly, finishing thoughts and sentences, and with enthusiasm? Did the speaker maintain the interest of the judge throughout the duration of the presentation?
8. Written feedback to be shared with the presenter (after the retreat)