Engineered Response To A Faux Dopamine | October 5, 2009 Issue - Vol. 87 Issue 40 | Chemical & Engineering News
Volume 87 Issue 40 | p. 37 | Concentrates
Issue Date: October 5, 2009

Engineered Response To A Faux Dopamine

Mutating one amino acid in a dopamine receptor makes a new tool for dissecting brain signals
Department: Science & Technology
Keywords: dopamine, G-protein-coupled receptor (GPCR), schizophrenia, Parkinson?s disease, molecular probes
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By engineering a dopamine receptor to respond only to an artificial ligand, researchers may have opened new avenues for studying neurotransmission. Malfunctioning dopamine signaling underlies schizophrenia and other diseases, so researchers are eager to understand the process. Dopamine receptors are G-protein-coupled receptors, and one way researchers learn more about this class of proteins is to retool them so they ignore their natural binding partners in favor of an artificial ligand. Such engineered proteins, called receptors activated solely by synthetic ligands (RASSLs), are valuable complements to genetic knockouts for studying signaling. However, a RASSL for a dopamine receptor has proven elusive. Peter Gmeiner and colleagues at Friedrich Alexander University, in Erlangen, Germany, have now identified the first RASSL for a dopamine receptor (ACS Chem. Neurosci., DOI: 10.1021/cn900001b). By changing a key phenyl­alanine residue to a bulkier tryptophan, the team abolished the receptor’s binding affinity for dopamine. With FAUC 185, a synthetic ligand they developed, the team showed they can activate the mutant do­pamine receptor in vitro.

 
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