Amino acid sensor conserved from bacteria to humans

Proc Natl Acad Sci U S A. 2022 Mar 8;119(10):e2110415119. doi: 10.1073/pnas.2110415119. Epub 2022 Mar 1.

Abstract

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.

Keywords: evolution; gabapentin; ion channels; serine/threonine kinases; signal transduction.

MeSH terms

  • Amino Acid Motifs
  • Archaea / chemistry*
  • Archaea / metabolism
  • Archaeal Proteins / chemistry*
  • Archaeal Proteins / metabolism
  • Bacteria / chemistry*
  • Bacteria / metabolism
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / metabolism
  • Humans
  • Membrane Proteins / chemistry*
  • Membrane Proteins / metabolism

Substances

  • Archaeal Proteins
  • Bacterial Proteins
  • CACHD1 protein, human
  • Membrane Proteins