title: Purification, pH-dependent conformational change, aggregation, and secretory granule membrane binding property of secretogranin II (chromogranin C).
abstract: Secretogranin II (SgII) is one of the three major proteins, the other two being chromogranins A (CGA) and B (CGB), of secretory granules of neuroendocrine cells. The Ca(2+) storage proteins CGA and CGB not only are coupled to the IP(3) receptor (IP(3)R)/Ca(2+) channels that exist on the secretory granule membrane but also are known to play key roles in secretory granule biogenesis. Unlike the better studied CGA and CGB, secretogranin II has never been completely purified in the native state and studied. We have therefore purified SgII in native form from bovine adrenal medulla and subjected it to biochemical characterization. Secretogranin II consisted of largely beta-sheet and random coil structures with a low level of alpha-helicity. Like CGA and CGB, it also underwent pH-dependent conformational changes, showing 9.5% alpha-helicity at pH 7.5 and 17.0% alpha-helicity at pH 5.5. Secretogranin II also underwent acidic pH- and Ca(2+)-dependent aggregation, and it was approximately 8-fold more sensitive than CGA to Ca(2+) in its pH-dependent aggregation but was 8-fold less sensitive than CGB. Further, similar to CGA and CGB that had interacted with the secretory granule membrane at the intragranular pH 5.5, SgII also interacted with the secretory granule membrane at pH 5.5 and dissociated from it at near-physiological pH 7.5, implying similar roles of SgII in the cell as those of CGA and CGB. Secretogranin II hence appeared to actively participate in secretory granule biogenesis as has been proposed for CGA and CGB.
authors.affiliation: National Creative Research Initiative Center for Secretory Granule Research, Korea Advanced Institute of Science and Technology, Yu Sung Gu, Dae Jeon, Korea 305-701.
authors.forename: Hee Yun
authors.initials: HY
authors.lastname: Park
authors.forename: Seung Ho
authors.initials: SH
authors.lastname: So
authors.forename: Woo Bok
authors.initials: WB
authors.lastname: Lee
authors.forename: Soon Hee
authors.initials: SH
authors.lastname: You
authors.forename: Seung Hyun
authors.initials: SH
authors.lastname: Yoo
mesh_terms: D000313:Adrenal Medulla / Q000378:metabolism; D000818:Animals; D002417:Cattle; D002850:Chromatography, Gel; D002864:Chromogranins; D015180:Electrophoresis, Gel, Two-Dimensional; D006863:Hydrogen-Ion Concentration; D011485:Protein Binding; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism; D022142:Secretory Vesicles / Q000378:metabolism*
chemical_list: D002864:Chromogranins; D011506:Proteins