Binding of calcium ions and SNAP-25 to the hexa EF-hand protein secretagogin

Annika Rogstam, Sara Linse, Anders Lindqvist, Peter James, Ludwig Wagner, Tord Berggård

Research output: Contribution to journalArticlepeer-review

68 Citations (SciVal)

Abstract

Secretagogin is a hexa EF-hand protein, which has been identified as a novel potential tumour marker. In the present study, we show that secretagogin binds four Ca2+ ions (log K-1 = 7.1 +/- 0.4, log K-2 = 4.7 +/- 0.6, log K-3 = 3.6 +/- 0.7 and log K-4 = 4.6 +/- 0.6 in physiological salt buffers) with a [Ca2+](0.5) of approx. 25 mu M. The tertiary structure of secretagogin changes significantly upon Ca2+ binding, but not upon Mg2+ binding, and the amount of exposed hydrophobic surface in secretagogin increases upon Ca2+ binding, but not upon Mg2+ binding. These properties suggest that secretagogin belongs to the 'sensor' family of Ca2+-binding proteins. However, in contrast with the prototypical Ca2+ sensor calmodulin, which interacts with a very large number of proteins, secretagogin is significantly less promiscuous. Only one secretagogin-interacting protein was reproducibly identified from insulinoma cell lysates and from bovine and mouse brain homogenates. This protein was identified as SNAP-25 (25 kDa synaptosome-associated protein), a protein involved in Ca2+-induced exocytosis in neurons and in neuroendocrine cells. K-d was determined to be 1.2 x 10(-7) M in the presence of Ca2+ and 1.5 x 10(-6) M in the absence of Ca2+. The comparatively low Ca2+ affinity for secretagogin and the fact that it undergoes Ca2+-induced conformational changes and interacts with SNAP-25 raise the possibility that secretagogin may link Ca2+ signalling to exocytotic processes.
Original languageEnglish
Pages (from-to)353-363
JournalBiochemical Journal
Volume401
Issue numberPt 1
DOIs
Publication statusPublished - 2007

Bibliographical note

The information about affiliations in this record was updated in December 2015.
The record was previously connected to the following departments: Department of Immunotechnology (011029300), Biophysical Chemistry (LTH) (011001011), Department of Cell and Organism Biology (Closed 2011.) (011002100), Islet cell physiology (013212142)

Subject classification (UKÄ)

  • Biochemistry and Molecular Biology

Keywords

  • secretagogin
  • conformational change
  • 25 kDa
  • sensor
  • calcium binding
  • synaptosome-associated protein (SNAP-25)
  • EF-hand

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