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Folding related dimerization of human cystatin C

Ekiel, Irena and Abrahamson, Magnus LU (1996) In Journal of Biological Chemistry 271(3). p.1314-1321
Abstract
With the aim to improve our understanding of the structural basis for protein self-association and aggregation, in particular in relationship to protein refolding and amyloid formation, folding-related processes for human cystatin C have been studied. Using NMR spectroscopy together with chromatographic and electrophoretic methods, a self-association process resulting in dimer formation for protein samples treated with denaturing agents as well as for samples subjected to low pH or high temperature conditions could be studied with amino acid resolution. In all three cases, the dimerization involves properly folded molecules and proceeds via the reactive site of the inhibitor, which leads to complete loss of its biological activity. This... (More)
With the aim to improve our understanding of the structural basis for protein self-association and aggregation, in particular in relationship to protein refolding and amyloid formation, folding-related processes for human cystatin C have been studied. Using NMR spectroscopy together with chromatographic and electrophoretic methods, a self-association process resulting in dimer formation for protein samples treated with denaturing agents as well as for samples subjected to low pH or high temperature conditions could be studied with amino acid resolution. In all three cases, the dimerization involves properly folded molecules and proceeds via the reactive site of the inhibitor, which leads to complete loss of its biological activity. This dimerization process has potential relevance for amyloid formation by the brain hemorrhage-causing Leu-Gln variant of cystatin C. The results also indicate that cystatin C dimerization and inactivation may occur in acidified compartments in vivo, which could be relevant for the physiological regulation of cysteine proteinase activity. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
271
issue
3
pages
1314 - 1321
publisher
ASBMB
external identifiers
  • scopus:0030052426
ISSN
1083-351X
language
English
LU publication?
yes
id
4ff789a4-1810-40da-8e53-8775de8ae102 (old id 1111055)
alternative location
http://www.jbc.org/cgi/content/full/271/3/1314
date added to LUP
2008-07-23 08:22:16
date last changed
2017-08-06 03:43:15
@article{4ff789a4-1810-40da-8e53-8775de8ae102,
  abstract     = {With the aim to improve our understanding of the structural basis for protein self-association and aggregation, in particular in relationship to protein refolding and amyloid formation, folding-related processes for human cystatin C have been studied. Using NMR spectroscopy together with chromatographic and electrophoretic methods, a self-association process resulting in dimer formation for protein samples treated with denaturing agents as well as for samples subjected to low pH or high temperature conditions could be studied with amino acid resolution. In all three cases, the dimerization involves properly folded molecules and proceeds via the reactive site of the inhibitor, which leads to complete loss of its biological activity. This dimerization process has potential relevance for amyloid formation by the brain hemorrhage-causing Leu-Gln variant of cystatin C. The results also indicate that cystatin C dimerization and inactivation may occur in acidified compartments in vivo, which could be relevant for the physiological regulation of cysteine proteinase activity.},
  author       = {Ekiel, Irena and Abrahamson, Magnus},
  issn         = {1083-351X},
  language     = {eng},
  number       = {3},
  pages        = {1314--1321},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {Folding related dimerization of human cystatin C},
  volume       = {271},
  year         = {1996},
}