biostudies-literatureGumerov VMHHS | National Institutes of HealthNIDCR NIH HHSSpanish Ministry of Science and InnovationWellcome TrustNIGMS NIH HHSe2110415119https://www.ebi.ac.uk/biostudies/studies/S-EPMC8915833biostudies-literatureUnknown119(10)SignificanceAmino acids are the building blocks of life and important signaling molecules. Despite their common structure, no universal mechanism for amino acid recognition by cellular receptors is currently known. We discovered a simple motif, which binds amino acids in various receptor proteins from all major life-forms. In humans, this motif is found in subunits of calcium channels that are implicated in pain and neurodevelopmental disorders. Our findings suggest that γ-aminobutyric acid-derived drugs bind to the same motif in human proteins that binds natural ligands in bacterial receptors, thus enabling future improvement of important drugs.Proceedings of the National Academy of Sciences of the United States of AmericaAmino acid sensor conserved from bacteria to humans.PMC8915833206279/Z/17/ZR01 DE024463PID2019-103972GA-100R35 GM131760206279PID2020-112612GB-100206279\Z\17\Z1R35GM131760Gumerov VMPage KMAndrianova EPZhulin IBMatilla MADolphin ACMonteagudo-Cascales EKrell TfalseAmino acid sensor conserved from bacteria to humans.SignificanceAmino acids are the building blocks of life and important signaling molecules. Despite their common structure, no universal mechanism for amino acid recognition by cellular receptors is currently known. We discovered a simple motif, which binds amino acids in various receptor proteins from all major life-forms. In humans, this motif is found in subunits of calcium channels that are implicated in pain and neurodevelopmental disorders. Our findings suggest that γ-aminobutyric acid-derived drugs bind to the same motif in human proteins that binds natural ligands in bacterial receptors, thus enabling future improvement of important drugs.2022-01-01T00:00:00Z2022 Mar2026-05-09T23:46:34.733Z2025-04-04T22:15:17.686ZS-EPMC89158333523863810.1073/pnas.2110415119