title: Nature of the pH-induced conformational changes and exposure of the C-terminal region of chromogranin A.
abstract: Chromogranin A is known to undergo pH induced conformational changes, and the difference in conformation is supposed to be responsible for the difference in Ca2+ binding property. To gain insight regarding the overall structure and the nature of pH-induced conformational changes of chromogranin A, limited trypsin digestions were carried out at pH 5.5 and pH 7.5. The resulting fragments were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and the amino acid sequences of the tryptic fragments were determined. From these analyses it was shown that the chromogranin A structure consists of an N-terminal compact core region and a rather loosely organized C-terminal region and that the change of pH from 7.5 to 5.5 loosened the overall structure of chromogranin A, exposing the C-terminal region. Since the conserved C-terminal region (residues 407-431) was shown to exist in monomer-dimer and monomer-tetramer equilibria at pH 7.5 and 5.5, respectively, the conformational changes of the region at pH 7.5 and 5.5 were studied by circular dichroism spectroscopy using a synthetic peptide representing the conserved C-terminal region. When the pH was changed from 7.5 to 5.5, the coil structure of the C-terminal peptide decreased with an accompanying increase of alpha-helicity.
authors.affiliation: Laboratory of Cellular Biology, National Institute of Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892.
authors.forename: S H
authors.initials: SH
authors.lastname: Yoo
authors.forename: J A
authors.initials: JA
authors.lastname: Ferretti
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D053379:Chromogranin A; D002864:Chromogranins / Q000737:chemistry*; D002942:Circular Dichroism; D006863:Hydrogen-Ion Concentration; D008969:Molecular Sequence Data; D011487:Protein Conformation; D014357:Trypsin
chemical_list: D053379:Chromogranin A; D002864:Chromogranins; D014357:Trypsin