Role of the hydrophobic transmembrane domain in membrane anchoring of endothelin-converting enzyme-1a

Endothelin-converting enzyme-1 (ECE-1) is a type II membrane protein that cleaves big endothelin-1 (big ET-1) to endothelin-1 (ET-1). The role of the N-terminal and membrane-spanning signal anchor domains in the biosynthesis and function of ECE-1 isoforms, ECE-1a, ECE-1b and ECE-1c, remains unknown. This study provides evidence that the deletion of the cytoplasmic N-terminal tail (residues 1-55) of bovine ECE-1a results in the processing of a putative signal peptide located in the signal anchor domain leading to the partial secretion of the recombinant enzyme into the media. The truncation of N-terminal and/or signal anchor domain does not affect the activity of ECE-1a. These results indicate that the hydrophobic signal anchor domain alone is not sufficient for the membrane anchoring of ECE-1a and that the N-terminal domain of ECE-1a is important for membrane targeting as well as the intracellular localization of the enzyme.