Can the Partial Peptide SIVSF of the β2-Adrenergic Receptor Recognize Chirality of the Epinephrine Neurotransmitter?

Chirality plays an essential role in biological molecular recognition, such as neurotransmission. Here, we applied electrospray-cold ion trap spectroscopy to complexes of a partial binding motif SIVSF of a β2-adrenergic receptor pocket with L- and D-epinephrine AdH+. The ultraviolet spectrum of the SIVSF-AdH+ complex changed drastically when L-AdH+ was replaced by its enantiomer. The isomer-selected infrared spectra revealed that D-AdH+ was bound to SIVSF by its protonated amino-group or a single catechol OH and induced nonhelical secondary structures of SIVSF. This is in sharp contrast to the helical SIVSF complex with L-AdH+, which is close to the natural binding structure with two catechol OHs binding in the receptor. This shows that a short pentapeptide SIVSF can distinguish the chirality of the ligand AdH+ as well as the receptor. This stereoselectivity is suggested to arise from an additional interaction involving the hydroxyl group on the chiral carbon.