BOKU - Universität für Bodenkultur Wien - Forschungsinformationssystem

Logo BOKU-Forschungsportal

Gewählte Publikation:

Müntener, K; Willimann, A; Zwicky, R; Svoboda, B; Mach, L; Baici, A.
(2005): Folding competence of N-terminally truncated forms of human procathepsin B.
J Biol Chem. 2005; 280(12):11973-11980 FullText FullText_BOKU

Abstract:
Besides acting as an inhibitor, the propeptide of human cathepsin B exerts an important auxiliary function as a chaperone in promoting correct protein folding. To explore the ability of N-terminally truncated forms of procathepsin B to fold into enzymatically active proteins, we produced procathepsin B variants progressively lacking N-terminal structural elements in baculovirus-infected insect cells. N-terminal truncation of the propeptide by up to 22 amino acids did not impair the production of activable procathepsin B. Secreted forms lacking the first 20, 21, or 22 amino acids spontaneously generated mature cathepsin B through autocatalytic processing, demonstrating that the first alpha-helix (Asp(11)-Arg(20)) is necessary for efficient inhibition of the enzyme by its propeptide. In contrast, proenzymes lacking the N-terminal part including the first beta-sheet (Trp(24)-Ala(26)) of the propeptide or containing an amino acid mutation directly preceding this beta-sheet were no longer properly folded. This shows that interactions between Trp(24) of the propeptide and Tyr(183), Tyr(188), and Phe(180) of the mature enzyme are important for stabilization and essential for procathepsin B folding. Thus, proenzyme forms missing more than the N-terminal 22 amino acids of the propeptide (notably truncated cathepsin B produced by the mRNA splice variant lacking exons 2 and 3, resulting in a propeptide shortened by 34 amino acids) are devoid of proteolytic activity because they cannot fold correctly. Thus, any pathophysiological involvement of truncated cathepsin B must be ascribed to properties other than proteolysis.
Autor*innen der BOKU Wien:
Mach Lukas
Find related publications in this database (using NML MeSH Indexing)
Animals -
Cathepsin B - chemistry
Cytosol - enzymology
Enzyme Precursors - chemistry
Glycosylation - chemistry
Humans - chemistry
Protein Folding - chemistry
Protein Structure, Secondary - chemistry
Recombinant Proteins - chemistry
Spodoptera - chemistry



Altmetric:
© BOKU Wien Impressum