Physico-chemical properties of the N-terminally truncated L68Q cystatin C found in amyloid deposits of brain haemorrhage patients

Biological Chemistry
B Gerhartz, M Abrahamson

Abstract

Cystatin C, a major extracellular cysteine proteinase inhibitor, is deposited as amyloid in brain haemorrhage patients with hereditary cystatin C amyloid angiopathy (HCCAA). A disease-causing mutation on the genetic level results in the substitution Leu68-->Gln (L68Q) in cystatin C, which causes protein instability. Besides carrying the L68Q substitution, cystatin C in amyloid deposits isolated from patients is N-terminally truncated by 10 amino acids. To elucidate the role of the N-terminal truncation for protein stability and aggregation properties, (delta1-10,L68Q)-cystatin C was produced in an Escherichia coli expression system and characterised. Unlike wild-type cystatin C, this variant rapidly dimerised under physiological conditions. Two unfolding intermediates of (delta1-10,L68Q)-cystatin C were identified, under the same pH and ionic strength conditions as required to form intermediates of full-length L68Q cystatin C. No evidence was found that the N-terminal truncation per se alters protein stability and leads to higher forms of aggregation. Monomeric as well as dimeric L68Q cystatin C incubated with neutrophil elastase was truncated as in HCCAA patients' amyloid. A protein variant with a thrombin cleavage site placed...Continue Reading

References

Jan 1, 1990·Virchows Archiv. A, Pathological Anatomy and Histopathology·E BenedikzG Gudmundsson
Sep 10, 1988·Lancet·A PalsdottirO Jensson
May 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·J GhisoB Frangione
Aug 1, 1987·Acta Neurologica Scandinavica·O JenssonB Frangione
Feb 15, 1994·Proceedings of the National Academy of Sciences of the United States of America·M Abrahamson, A Grubb
Jan 19, 1996·The Journal of Biological Chemistry·I Ekiel, M Abrahamson
Aug 15, 1997·Journal of Molecular Biology·I EkielK Gehring
Apr 8, 1999·Molecular Pathology : MP·M BjarnadottirM Abrahamson

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Citations

Aug 18, 2004·Journal of Molecular Biology·Robert JanowskiMariusz Jaskolski
Dec 18, 2004·Critical Reviews in Clinical Laboratory Sciences·Michele Mussap, Mario Plebani
Jan 27, 2006·Annals of Neurology·David N IraniAvindra Nath
Feb 7, 2014·The Journal of Biological Chemistry·Sandra WhellyGail A Cornwall

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