Identification of the secretory vesicle membrane binding region of chromogranin A

Since the conserved near N-terminal region (residues 18-37) of chromogranin A (CGA) has tentatively been identified as the vesicle membrane interacting region using synthetic peptides, it was necessary to confirm this finding with CGA deletion proteins. In order to address this need and to clarify the discrepancies of the published amino acid sequences of CGA, we cloned a CGA gene and produced CGA deletion proteins of various sizes. The recombinant CGA protein lacking the first 16 amino acid residues bound to the vesicle membrane as well as the full-length CGA at pH 5.5. However, the CGA protein lacking the first 39 amino acid residues, which include the conserved near N-terminal region (residues 17-38), failed to interact with the vesicle membrane at pH 5.5, clearly indicating the essential role of the conserved near N-terminal region in the pH-dependent interaction of CGA with the vesicle membrane.