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Web Date: September 29, 2009

Responding To Faux Dopamine

Neurochemistry: Mutating one amino acid makes a new tool for dissecting brain signals
Department: Science & Technology
Keywords: G-protein-coupled receptor (GPCR), schizophrenia, Parkinson's, 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. Now, Peter Gmeiner and colleagues at Friedrich Alexander University, in Erlangen, Germany, have 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 could activate the mutant dopamine receptor in vitro.

 
Chemical & Engineering News
ISSN 0009-2347
Copyright © American Chemical Society

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