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

Rogstam, Annika LU ; Linse, Sara LU ; Lindqvist, Anders LU ; James, Peter LU ; Wagner, Ludwig and Berggård, Tord LU (2007) In Biochemical Journal 401(Pt 1). p.353-363
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
secretagogin, conformational change, 25 kDa, sensor, calcium binding, synaptosome-associated protein (SNAP-25), EF-hand
in
Biochemical Journal
volume
401
issue
Pt 1
pages
353 - 363
publisher
Portland Press Limited
external identifiers
  • wos:000243538800036
  • scopus:33846299257
ISSN
0264-6021
DOI
10.1042/BJ20060918
language
English
LU publication?
yes
id
aeecb94a-20ac-411a-b3a1-81adb95f3736 (old id 677565)
date added to LUP
2007-12-14 12:36:28
date last changed
2017-10-08 04:22:13
@article{aeecb94a-20ac-411a-b3a1-81adb95f3736,
  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.},
  author       = {Rogstam, Annika and Linse, Sara and Lindqvist, Anders and James, Peter and Wagner, Ludwig and Berggård, Tord},
  issn         = {0264-6021},
  keyword      = {secretagogin,conformational change,25 kDa,sensor,calcium binding,synaptosome-associated protein (SNAP-25),EF-hand},
  language     = {eng},
  number       = {Pt 1},
  pages        = {353--363},
  publisher    = {Portland Press Limited},
  series       = {Biochemical Journal},
  title        = {Binding of calcium ions and SNAP-25 to the hexa EF-hand protein secretagogin},
  url          = {http://dx.doi.org/10.1042/BJ20060918},
  volume       = {401},
  year         = {2007},
}