An aspartate conserved among G-protein receptors confers allosteric regulation of alpha 2-adrenergic receptors by sodium.
The residue involved in sodium regulation of G-protein-coupled receptors has been identified by site-directed mutagenesis of the alpha 2-adrenergic receptor gene. Mutation of Asp-79 to Asn-79 entirely eliminates allosteric regulation of ligand binding by monovalent cations without perturbing the selectivity of adrenergic binding or allosteric modulation of that binding by amiloride analogs. The high degree of conservation of this aspartate residue in all G-protein-coupled receptors, without even a conservative change to glutamate, underscores the probable importance of this allosteric regulation.
Horstman
D A
DA
Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-6600.
Brandon
S
S
Wilson
A L
AL
Guyer
C A
CA
Cragoe
E J
EJ
Limbird
L E
LE
D000345:Affinity Labels; D000494:Allosteric Regulation; D000595:Amino Acid Sequence; D000818:Animals; D001224:Aspartic Acid / Q000502:physiology*; D000068438:Brimonidine Tartrate; D004252:DNA Mutational Analysis; D004146:Dioxanes / Q000378:metabolism; D004837:Epinephrine / Q000378:metabolism; D019329:Idazoxan; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D010109:Oxymetazoline / Q000378:metabolism; D011224:Prazosin / Q000378:metabolism; D011810:Quinoxalines / Q000378:metabolism; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D012964:Sodium / Q000502:physiology*; D013329:Structure-Activity Relationship; D013552:Swine; D014162:Transfection; D015016:Yohimbine / Q000378:metabolism
D000345:Affinity Labels; D004146:Dioxanes; D011810:Quinoxalines; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D001224:Aspartic Acid; D000068438:Brimonidine Tartrate; D010109:Oxymetazoline; D012964:Sodium; D011224:Prazosin; D019329:Idazoxan; D004837:Epinephrine