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

Author:
  • Annika Rogstam
  • Sara Linse
  • Anders Lindqvist
  • Peter James
  • Ludwig Wagner
  • Tord Berggård
Publishing year: 2007
Language: English
Pages: 353-363
Publication/Series: Biochemical Journal
Volume: 401
Issue: Pt 1
Document type: Journal article
Publisher: Portland Press Limited

Abstract english

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.

Keywords

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

Other

Published
  • Islet cell physiology
  • ISSN: 0264-6021
Peter James
E-mail: peter.james [at] immun.lth.se

Professor

Department of Immunotechnology

+46 46 222 14 96

+46 70 247 79 60

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