Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board Member: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Sies, Helmut / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred

12 Issues per year


IMPACT FACTOR 2016: 3.273

CiteScore 2016: 3.01

SCImago Journal Rank (SJR) 2016: 1.679
Source Normalized Impact per Paper (SNIP) 2016: 0.800

Online
ISSN
1437-4315
See all formats and pricing
More options …
Volume 386, Issue 11 (Nov 2005)

Issues

Proinsulin lacking the A7-B7 disulfide bond, Ins2Akita, tends to aggregate due to the exposed hydrophobic surface

Takeo Yoshinaga
  • Department of Health and Environmental Sciences, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Keisuke Nakatome
  • Department of Health and Environmental Sciences, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Jun-ichi Nozaki
  • Department of Health and Environmental Sciences, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Motoko Naitoh
  • Department of Molecular and Cellular Biology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8397, Japan
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Jun Hoseki
  • Department of Molecular and Cellular Biology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8397, Japan and Core Research for Evolutional Science/Japan Science Technology Agency (CREST/JST), Kawaguchi, Saitama 332-0012, Japan
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Hiroshi Kubota
  • Department of Molecular and Cellular Biology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8397, Japan and Core Research for Evolutional Science/Japan Science Technology Agency (CREST/JST), Kawaguchi, Saitama 332-0012, Japan
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Kazuhiro Nagata
  • Department of Molecular and Cellular Biology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8397, Japan and Core Research for Evolutional Science/Japan Science Technology Agency (CREST/JST), Kawaguchi, Saitama 332-0012, Japan
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Akio Koizumi
  • Department of Health and Environmental Sciences, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2005-11-24 | DOI: https://doi.org/10.1515/BC.2005.124

Abstract

A single mutation (C96Y) in the Ins2 gene, which disrupts the A7-B7 disulfide bond, causes the diabetic phenotype in Akita mice. We biochemically analyzed the conformation of wild-type and Akita mutant recombinant proinsulins. Gel filtration chromatography and dynamic light scattering revealed that the apparent size of the mutant proinsulin molecules was significantly larger than that of wild-type proinsulin, even in the absence of intermolecular disulfide bonds. Titration with a hydrophobic probe, 1-anilinonaphthalene-8-sulfonate, demonstrated that the mutant proinsulin was more hydrophobic than the wild type. In addition, circular dichroism studies revealed that the conformation of the mutant proinsulin was less stable than the wild type, which is consistent with the observation that hydrophobic residues are exposed on the surface of the proinsulin molecules. Studies with antiserum against the C-peptide of proinsulin indicated that the mutant proinsulin had an immunoreactivity that was at least one-tenth weaker than wild-type proinsulin, suggesting that the C-peptide of mutant proinsulin is buried inside the aggregate of the proinsulin molecule. These findings indicate that increased hydrophobicity of mutant proinsulin facilitates aggregate formation, providing a clue to the dominant negative effect in the Akita mouse.

Keywords: aggregation; β-cell dysfunction; C96Y mutation of diabetes; disulfide bond; hydrophobic surface; Ins2Akita

About the article

Corresponding author


Received: February 21, 2005

Accepted: August 11, 2005

Published Online: 2005-11-24

Published in Print: 2005-11-01


Citation Information: Biological Chemistry, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/BC.2005.124.

Export Citation

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

[1]
Changcheng Zhou, Brian Pridgen, Nakesha King, Jinxian Xu, and Jan L. Breslow
Journal of Lipid Research, 2011, Volume 52, Number 8, Page 1483
[2]
Michael D. Dennis, Tabitha L. Schrufer, Sarah K. Bronson, Scot R. Kimball, and Leonard S. Jefferson
Journal of Biological Chemistry, 2011, Volume 286, Number 39, Page 34286
[3]
Michael A. Weiss
Journal of Biological Chemistry, 2009, Volume 284, Number 29, Page 19159
[4]
Florin Despa and R. Stephen Berry
Journal of Diabetes Science and Technology, 2010, Volume 4, Number 6, Page 1447
[5]
Parveen Salahuddin, Mohammad Khursheed Siddiqi, Sanaullah Khan, Ali Saber Abdelhameed, and Rizwan Hasan Khan
Journal of Molecular Structure, 2016, Volume 1123, Page 311
[6]
K. He, C. N. Cunningham, N. Manickam, M. Liu, P. Arvan, and B. Tsai
Molecular Biology of the Cell, 2015, Volume 26, Number 19, Page 3413
[7]
E. L. Edghill, S. E. Flanagan, A.-M. Patch, C. Boustred, A. Parrish, B. Shields, M. H. Shepherd, K. Hussain, R. R. Kapoor, M. Malecki, M. J. MacDonald, J. Stoy, D. F. Steiner, L. H. Philipson, G. I. Bell, A. T. Hattersley, and S. Ellard
Diabetes, 2008, Volume 57, Number 4, Page 1034
[8]
M. Liu, I. Hodish, C. J. Rhodes, and P. Arvan
Proceedings of the National Academy of Sciences, 2007, Volume 104, Number 40, Page 15841
[9]
Michael A. Weiss
FEBS Letters, 2013, Volume 587, Number 13, Page 1942
[10]
F. Despa
Biophysical Chemistry, 2009, Volume 140, Number 1-3, Page 115
[11]
[12]
Constantin Ionescu-Tirgoviste and Florin Despa
Integr. Biol., 2011, Volume 3, Number 3, Page 173
[13]
Thomas Waterfield and Anna L Gloyn
Pediatric Health, 2008, Volume 2, Number 4, Page 517
[14]
Akio KOIZUMI
Nippon Eiseigaku Zasshi (Japanese Journal of Hygiene), 2010, Volume 65, Number 1, Page 37

Comments (0)

Please log in or register to comment.
Log in