The primary structure of bovine chromogranin A: a representative of a class of acidic secretory proteins common to a variety of peptidergic cells

Abstract

We have determined the primary structure of bovine chromogranin A as a first step in the elucidation of the function of this widespread protein. After oligonucleotide screening of a cDNA library of bovine adrenal medulla, a clone (insert length 1.9 kb) containing the entire coding region for chromogranin A was isolated and sequenced. The authenticity of the sequence was verified by comparison with N-terminal, several internal, and C-terminal amino acid sequences as well as the amino acid composition of chromogranin A. The cDNA clone hybridized to an mRNA of 2.1 kb and, after in vitro transcription-translation, yielded a polypeptide with a similar electrophoretic mobility in SDS gels to chromogranin A. The polypeptide chain of chromogranin A comprises 431 amino acid residues, corresponding to an unmodified protein of 48 kd, and is preceded by a cleaved signal peptide of 18 amino acid residues. Interesting features of the chromogranin A structure include repeated clusters of glutamic acid residues, the occurrence of eight potential dibasic cleavage sites, six of which are located in the C-terminal domain, and the presence, in the N-terminal domain, of -Arg-Gly-Asp- (RGD), a three amino acid sequence involved in the binding of several constitutively secreted proteins to cell membranes.