Identifying the biological role of lipid binding to zinc α2 glycoprotein in lipolysis

Prof Stephen J Perkins (primary)
Structural and Molecular Biology
University College London
Dr Alun R. Coker (secondary)
Crystallography Facility, Rayne Institute
University College London


Zinc-α2-glycoprotein [ZAG, 42kDa] is an adipokine and regulator of body fat mass involved in fat cell lipolysis by an unknown mechanism. Identifying its true biological ligand will address a key BBSRC research topic on diet and health. Following our LIDO-supported crystal structure for the first ZAG-fatty acid complex [front cover, Biochem J] and mutagenesis/screening of its binding site [in revision], we will elucidate how specific ZAG is for binding dietary signaling lipids. Lipid binding will be tested by state-of-the-art mass spectrometry, ZAG-lipid co-crystals will reveal molecular details of the lipid-ZAG interaction, and surface plasmon resonance will give lipid binding affinities.


SUBMITTED – Zahid, H., Lau, A. M., Kelly, S. M., Gor, J., Perkins, S. J. & McDermott, L. C. [2020] Identification of diverse lipid-binding modes in the groove of zinc-α2-glycoprotein reveals its functional versatility. FEBS Journal. In revision for acceptance.
Lau, A. M., Zahid, H., Gor, J., Perkins, S. J., Coker, A. R. & McDermott, L. C. [2019] Crystal structure of zinc-α2-glycoprotein in complex with a fatty acid reveals multiple different modes of lipid binding. Biochem. J. 476, 2815-2834. JOURNAL FRONT COVER
Zahid, H., Miah, L., Brochard, L., Lau, A. M., Hati, D., Bui, T. T. T, Drake, A. F., Gor, J., Perkins, S. J. & McDermott, L. C. [2016] Zinc induced oligomerisation of zinc α2 glycoprotein reveals distinct fatty acid binding sites, Biochem J. 473, 43-54
Kumar AA, Hati D, Thaker TM, Miah L, Cunningham P, Domene C, Bui TT, Drake AF, & McDermott L.C. [2013] Strong and weak zinc binding sites in human zinc-α2-glycoprotein. FEBS Letters, 587, 3949-3954.
Delker, SL, West, AP, McDermott, L, Kennedy, MW, Bjorkman, PJ [2004] Crystallographic studies of ligand binding by Zn-alpha2-glycoprotein. Journal of Structural Biology, 148, 205-213.

Animal disease, health and welfare
Area of Biology
BiotechnologyStructural Biology
Techniques & Approaches
BiochemistryBioinformaticsBiophysicsChemistryImage ProcessingMolecular BiologySimulation / Modelling