liu.seSearch for publications in DiVA
Endre søk
RefereraExporteraLink to record
Permanent link

Direct link
Referera
Referensformat
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Prevention of domain swapping inhibits dimerization and amyloid fibril formation of cystatin C. Use of engineered disulfide bridges, antibodies, and carboxymethylpapain to stabilize the monomeric form of cystatin C
Department of Clinical Chemistry, University Hospital, S-22185 Lund, Sweden.
Department of Clinical Chemistry, University Hospital, S-22185 Lund, Sweden.
Department of Organic Chemistry, Faculty of Chemistry, University of Gdansk, J. Sobieskiego 18, 80-952 Gdansk, Poland.
Department of Crystallography, A. Mickiewicz University, Polish Academy of Sciences, Grunwaldzka 6, 60-780 Poznan, Poland.
Vise andre og tillknytning
2004 (engelsk)Inngår i: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 279, nr 23, 24236-24245 s.Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Amyloidogenic proteins like cystatin C and prion proteins have been shown to form dimers by exchange of subdomains of the monomeric proteins. This process, called "three-dimensional domain swapping," has also been suggested to play a part in the generation of amyloid fibrils. One variant of cystatin C, L68Q cystatin C, is highly amyloidogenic, and persons carrying the corresponding gene suffer from massive cerebral amyloidosis leading to brain hemorrhage and death in early adult life. The present work describes the production of two variants of wild type and L68Q cystatin C with disulfide bridges at positions selected to inhibit domain swapping without affecting the biological function of the four cystatin C variants as cysteine protease inhibitors. The capacity of the four variant proteins to form dimers was tested and compared with that of wild type and L68Q cystatin C. In contrast to the latter two proteins, all four protein variants stabilized by disulfide bridges were resistant toward the formation of dimers. The capacity of the two stabilized variants of wild type cystatin C to form amyloid fibrils was investigated and found to be reduced by 80% compared with that of wild type cystatin C. In an effort to investigate whether exogenous agents could also suppress the formation of dimers of wild type and L68Q cystatin C, a monoclonal antibody or carboxymethylpapain, an inactivated form of a cysteine protease, was added to systems inducing dimerization of wild type and L68Q cystatin C. It was observed that catalytic amounts of both the monoclonal antibody and carboxymethylpapain could suppress dimerization.

sted, utgiver, år, opplag, sider
2004. Vol. 279, nr 23, 24236-24245 s.
HSV kategori
Identifikatorer
URN: urn:nbn:se:liu:diva-45714DOI: 10.1074/jbc.M402621200OAI: oai:DiVA.org:liu-45714DiVA: diva2:266610
Tilgjengelig fra: 2009-10-11 Laget: 2009-10-11 Sist oppdatert: 2017-12-13

Open Access i DiVA

Fulltekst mangler

Andre lenker

Forlagets fulltekst

Personposter BETA

Westermark, Gunilla

Søk i DiVA

Av forfatter/redaktør
Westermark, Gunilla
Av organisasjonen
I samme tidsskrift
Journal of Biological Chemistry

Søk utenfor DiVA

GoogleGoogle Scholar

doi
urn-nbn

Altmetric

doi
urn-nbn
Totalt: 32 treff
RefereraExporteraLink to record
Permanent link

Direct link
Referera
Referensformat
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf