Dimerization and tetramerization properties of the C-terminal region of chromogranin A: a thermodynamic analysis.
Chromogranin A, which is a high-capacity, low-affinity Ca2+ binding protein, has recently been shown to exist in monomer-dimer and in monomer-tetramer equilibria at pH 7.5 and 5.5, respectively [Yoo, S. H., & Lewis, M. S. (1992) J. Biol. Chem. 267, 11236-11241]. The pH appeared to be a necessary and sufficient factor determining the types of oligomer formed. In the present study, using 14 synthetic peptides representing various portions of chromogranin A, we have identified a region in chromogranin A which exhibited dimerization and tetramerization properties at pH 7.5 and 5.5, respectively. Of the 14 peptides, only the conserved C-terminal region (residues 407-431), represented by peptide 14, showed the oligomerization property, existing in a dimeric state at pH 7.5 and in a tetrameric state at pH 5.5. The delta G degrees values of tetramerization were approximately -18.0 kcal/mol, and the delta G degrees value of dimerization was -4.6 kcal/mol. Although peptide 14 represented only 6% of the entire sequence, the delta G degrees value of -18.0 kcal/mol accounted for 80-83% of the delta G degrees values (-21.6 to -22.7 kcal/mol) of tetramerization of intact chromogranin A. Unlike the tetramerization mechanisms of intact chromogranin A where the presence of 35 mM Ca2+ changed the tetramerization mechanism from an enthalpically driven to an entropically driven reaction, the tetramerization mechanism of peptide 14 remained entropically driven regardless of the presence of Ca2+. Likewise, dimerization of the peptide was also entropically driven.(ABSTRACT TRUNCATED AT 250 WORDS)
Yoo
S H
SH
Laboratory of Cellular Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland 20892.
Lewis
M S
MS
D000595:Amino Acid Sequence; D053379:Chromogranin A; D002864:Chromogranins / Q000737:chemistry*; D002942:Circular Dichroism; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry; D013816:Thermodynamics; D014461:Ultracentrifugation
D053379:Chromogranin A; D002864:Chromogranins; D010446:Peptide Fragments