Nature of the pH‐induced conformational changes and exposure of the C‐terminal region of chromogranin A

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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 α‐helicity.