Open AccessRole of the Hydrophobic Transmembrane Domain in Membrane Anchoring of Endothelin-Converting Enzyme-1a
Author(s) -
Sharon Courtnie Brooks,
Adviye Ergul
Publication year - 2000
Publication title -
journal of cardiovascular pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.762
H-Index - 100
eISSN - 1533-4023
pISSN - 0160-2446
DOI - 10.1097/00005344-200036051-00012
Subject(s) - signal peptide , transmembrane domain , membrane , transmembrane protein , secretion , enzyme , intracellular , biochemistry , biophysics , endothelin 1 , chemistry , microbiology and biotechnology , biology , peptide sequence , receptor , gene
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.