Abstract
Functional advances have guided our knowledge of physiological and fatal pathological mechanisms of the hormone angiotensin II (AngII) and its antagonists. Such studies revealed that tissue response to a given dose of the hormone or its antagonist depends on receptors that engage the ligand. Thus, we need to know much more about the structures of receptor-ligand complexes at high resolution. Recently, X-ray structures of both AngII receptors (AT(1) and AT(2) receptors) bound to peptide and non-peptide ligands have been elucidated, providing new opportunities to examine the dynamic fluxes in the 3D architecture of the receptors, as the basis of ligand selectivity, efficacy, and regulation of the molecular functions of the receptors. Constituent structural motifs cooperatively transform ligand selectivity into specific functions, thus conceptualizing the primacy of the 3D structure over individual motifs of receptors. This review covers the new data elucidating the structural dynamics of AngII receptors and how structural knowledge can be transformative in understanding the mechanisms underlying the physiology of AngII.