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Tryptophan indole ¹⁵N–¹H signals are well separated in nuclear magnetic resonance (NMR) spectra of proteins. Assignment of the indole ¹⁵N–¹H signals therefore enables one to obtain site-specific information on complex proteins in supramacromolecular systems, even when extensive assignment of backbone ¹⁵N–¹H resonances is challenging. Here we exploit the unique indole ¹⁵N–¹H chemical shift by introducing extrinsic tryptophan reporter residues at judiciously chosen locations in a membrane protein for increased coverage of structure and function by NMR. We demonstrate this approach with three variants of the human A_2A adenosine receptor (A_2AAR), a class A G protein-coupled receptor, each containing a single extrinsic tryptophan near the receptor intracellular surface, in helix V, VI, or VII, respectively. We show that the native A_2AAR global protein fold and ligand binding activity are preserved in …