Identification of specific amino acids (Asp75 and Pro93) required for the stable complex formation of human ETB receptor with endothelin-1 provides molecular insights into receptor structure.
Does not guide ET receptor antagonist use; leaves open structure-guided ETBR ligand design in humans.
ETB type endothelin receptor (ETBR) forms a stable complex with its ligand endothelin-1 (ET-1). The ligand-receptor complex can survive in the presence of 2% SDS and migrate in SDS-polyacrylamide gel electrophoresis at reduced temperature. This is not the case for the ETA type endothelin receptor (ETAR). Most of ETBR from various animals, except rat, can form such a stable complex. Examination of stability in the ligand-receptor complex which was formed by chimeric receptors constructed from human ETBR and rat ETBR demonstrated that the region containing 29 amino acids in the N-terminal extracellular domain is responsible for the formation of such a stable complex. Site-directed mutagenesis focused on this particular region revealed that Asp75 and Pro93 are involved in the formation of the stable complex. This unique observation contributes to the elucidation of the structure of the stable ETBR.ET-1 complex at the molecular level.
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Takasuka et al. (1994) studied this question.