MUTATION OF A CONSERVED 5TH TRANSMEMBRANE DOMAIN LYSINE RESIDUE (LYS(215)) ATTENUATES LIGAND-BINDING IN THE ANGIOTENSIN-II TYPE-2 RECEPTOR

A fifth transmembrane domain lysine residue is conserved in both the t ype 1 (AT(1)) and type 2 (AT(2)) angiotensin II (AngII) receptors. Thi s lysine (Lys(199)) is believed to play a critical role in peptide bin ding for the AT(1) receptor. To evaluate its possible role in the AT(2 ) receptor, the analogous AT(2) residue (Lys(199)) was changed to glut amine. This mutation greatly reduced the affinity for both I-125-AngII and I-125-Sar(1),Ile(8)-AngII and abolished binding to the non-peptid e I-125-PD122979. These data indicate that despite a relatively low ho mology of 34%, some commonalities in the binding mechanism for AngII m ay exist between the two subtypes. (C) 1997 Elsevier Science B.V.