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.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Yoo SH,Ferretti JA

doi

10.1016/0014-5793(93)80715-7

subject

Has Abstract

pub_date

1993-11-22 00:00:00

pages

373-7

issue

3

eissn

0014-5793

issn

1873-3468

pii

0014-5793(93)80715-7

journal_volume

334

pub_type

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