The Serotonin G-Protein Coupled Receptor 5HT2A: Molecular and Multiple Sequence Analysis

The serotonin receptor is an integral part of human biochemistry, especially in regard to neuropsychiatric illness, but is also found across animal species. There is a need for a deeper molecular understanding of the serotonin receptor in regard to novel treatments in psychiatry. The present review and subsequent analysis provide detailed insight regarding the function, composition, and molecular interactions of the 5HT2A receptor and its associated G-protein complex. A multiple sequence analysis of the 5HT2A and Gaq proteins among four vertebrate species was performed to elucidate protein conservation across taxa. The sequence alignment demonstrated regions of high conservation across the entire length of the Gaq protein sequences and in specific regions of the 5HT2A receptor, including five alpha helices that interact with the Gaq protein. Chimera was used to examine the location and molecular level interactions of key 5HT2A and Gaq residues in the cryoEM structure of 5HT2A with mini-Gaq and beta/gamma (PDB 6WHA). This analysis provided additional insight into interactions around residues known to be important for function and allowed the identification of additional residues predicted to lead to anomalous function if mutated.