Quick Search:

uzh logo
Browse by:
bullet
bullet
bullet
bullet

Zurich Open Repository and Archive

Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-43089

Burkart, V; Siegenthaler, R K; Blasius, E; Vandenbroeck, K; Alloza, I; Fingberg, W; Schloot, N C; Christen, P; Kolb, H (2010). High affinity binding of hydrophobic and autoantigenic regions of proinsulin to the 70 kDa chaperone DnaK. BMC Biochemistry, 11:44.

[img]
Preview
PDF (Verlags-PDF)
1MB

View at publisher

Abstract

BACKGROUND: Chaperones facilitate proper folding of peptides and bind to misfolded proteins as occurring during periods of cell stress. Complexes of peptides with chaperones induce peptide-directed immunity. Here we analyzed the interaction of (pre)proinsulin with the best characterized chaperone of the hsp70 family, bacterial DnaK.

RESULTS: Of a set of overlapping 13-mer peptides of human preproinsulin high affinity binding to DnaK was found for the signal peptide and one further region in each proinsulin domain (A- and B-chain, C-peptide). Among the latter, peptides covering most of the B-chain region B11-23 exhibited strongest binding, which was in the range of known high-affinity DnaK ligands, dissociation equilibrium constant (K'd) of 2.2 ± 0.4 μM. The B-chain region B11-23 is located at the interface between two insulin molecules and not accessible in insulin oligomers. Indeed, native insulin oligomers showed very low DnaK affinity (K'd 67.8 ± 20.8 μM) whereas a proinsulin molecule modified to prevent oligomerization showed good binding affinity (K'd 11.3 ± 7.8 μM).

CONCLUSIONS: Intact insulin only weakly interacts with the hsp70 chaperone DnaK whereas monomeric proinsulin and peptides from 3 distinct proinsulin regions show substantial chaperone binding. Strongest binding was seen for the B-chain peptide B 11-23. Interestingly, peptide B11-23 represents a dominant autoantigen in type 1 diabetes.

Citations

1 citation in Web of Science®
2 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

111 downloads since deposited on 25 Jan 2011
71 downloads since 12 months

Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Department of Biochemistry
07 Faculty of Science > Department of Biochemistry
DDC:570 Life sciences; biology
Language:English
Date:2010
Deposited On:25 Jan 2011 17:55
Last Modified:27 Nov 2013 18:38
Publisher:BioMed Central
ISSN:1471-2091
Publisher DOI:10.1186/1471-2091-11-44
PubMed ID:21059249

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page