Zinc α2 glycoprotein (ZAG) is an adipokine with a class I MHC protein fold and is associated with obesity and diabetes. Although its intrinsic ligand remains unknown, ZAG binds the dansylated C11 fatty acid 11-(dansylamino)undecanoic acid (DAUDA) in the groove between the α1 and α2 domains. The surface of ZAG has approximately 15 weak zinc-binding sites deemed responsible for precipitation from human plasma. In the present study the functional significance of these metal sites was investigated. Analytical ultracentrifugation (AUC) and CD showed that zinc, but not other divalent metals, causes ZAG to oligomerize in solution. Thus ZAG dimers and trimers were observed in the presence of 1 and 2 mM zinc. Molecular modelling of X-ray scattering curves and sedimentation coefficients indicated a progressive stacking of ZAG monomers, suggesting that the ZAG groove may be occluded in these. Using fluorescence-detected sedimentation velocity, these ZAG–zinc oligomers were again observed in the presence of the fluorescent boron dipyrromethene fatty acid C16-BODIPY (4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-hexadecanoic acid). Fluorescence spectroscopy confirmed that ZAG binds C16-BODIPY. ZAG binding to C16-BODIPY, but not to DAUDA, was reduced by increased zinc concentrations. We conclude that the lipid-binding groove in ZAG contains at least two distinct fatty acid-binding sites for DAUDA and C16-BODIPY, similar to the multiple lipid binding seen in the structurally related immune protein CD1c. In addition, because high concentrations of zinc occur in the pancreas, the perturbation of these multiple lipid-binding sites by zinc may be significant in Type 2 diabetes where dysregulation of ZAG and zinc homoeostasis occurs.
Skip Nav Destination
Article navigation
January 2016
-
Cover Image
Cover Image
A pseudo-coloured TEM showing a blebbishield from RT4 bladder cancer cells. Courtesy of Goodwin G. Jinesh, Ashish M. Kamat and Kenneth Dunner Jr. (see Jinesh et al. pages 97–105 in this issue). - PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
- PDF Icon PDF LinkEditorial Board
Research Article|
December 09 2015
Zinc-induced oligomerization of zinc α2 glycoprotein reveals multiple fatty acid-binding sites
Henna Zahid;
Henna Zahid
1
*Diabetes and Nutritional Sciences Division, Franklin Wilkins Building, 150 Stamford Street, King's College London, London SE1 9NH, U.K.
†Department of Structural and Molecular Biology, University College London, Darwin Building, Gower Street, London WC1E 6BT, U.K.
Search for other works by this author on:
Layeque Miah;
Layeque Miah
1
*Diabetes and Nutritional Sciences Division, Franklin Wilkins Building, 150 Stamford Street, King's College London, London SE1 9NH, U.K.
Search for other works by this author on:
Andy M. Lau;
Andy M. Lau
*Diabetes and Nutritional Sciences Division, Franklin Wilkins Building, 150 Stamford Street, King's College London, London SE1 9NH, U.K.
†Department of Structural and Molecular Biology, University College London, Darwin Building, Gower Street, London WC1E 6BT, U.K.
Search for other works by this author on:
Lea Brochard;
Lea Brochard
†Department of Structural and Molecular Biology, University College London, Darwin Building, Gower Street, London WC1E 6BT, U.K.
Search for other works by this author on:
Debolina Hati;
Debolina Hati
*Diabetes and Nutritional Sciences Division, Franklin Wilkins Building, 150 Stamford Street, King's College London, London SE1 9NH, U.K.
Search for other works by this author on:
Tam T.T. Bui;
Tam T.T. Bui
‡Biomolecular Spectroscopy Centre, Optical and Chiroptical Spectroscopy Facility, The Wolfson Wing, Hodgkin Building, King's College London, London SE1 1UL, U.K.
Search for other works by this author on:
Alex F. Drake;
Alex F. Drake
‡Biomolecular Spectroscopy Centre, Optical and Chiroptical Spectroscopy Facility, The Wolfson Wing, Hodgkin Building, King's College London, London SE1 1UL, U.K.
Search for other works by this author on:
Jayesh Gor;
Jayesh Gor
†Department of Structural and Molecular Biology, University College London, Darwin Building, Gower Street, London WC1E 6BT, U.K.
Search for other works by this author on:
Stephen J. Perkins;
Stephen J. Perkins
†Department of Structural and Molecular Biology, University College London, Darwin Building, Gower Street, London WC1E 6BT, U.K.
Search for other works by this author on:
Lindsay C. McDermott
*Diabetes and Nutritional Sciences Division, Franklin Wilkins Building, 150 Stamford Street, King's College London, London SE1 9NH, U.K.
†Department of Structural and Molecular Biology, University College London, Darwin Building, Gower Street, London WC1E 6BT, U.K.
3To whom correspondence should be addressed (email [email protected]).
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
July 27 2015
Revision Received:
October 13 2015
Accepted:
October 20 2015
Accepted Manuscript online:
October 20 2015
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2016 Authors; published by Portland Press Limited
2016
Biochem J (2016) 473 (1): 43–54.
Article history
Received:
July 27 2015
Revision Received:
October 13 2015
Accepted:
October 20 2015
Accepted Manuscript online:
October 20 2015
Citation
Henna Zahid, Layeque Miah, Andy M. Lau, Lea Brochard, Debolina Hati, Tam T.T. Bui, Alex F. Drake, Jayesh Gor, Stephen J. Perkins, Lindsay C. McDermott; Zinc-induced oligomerization of zinc α2 glycoprotein reveals multiple fatty acid-binding sites. Biochem J 1 January 2016; 473 (1): 43–54. doi: https://doi.org/10.1042/BJ20150836
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.