Crystallographic studies of ligand binding by Zn-alpha(2)-glycoprotein
AuthorsDelker, Silvia L.
West, Anthony P.
McDermott, Lindsay C.
Kennedy, Malcolm W.
Bjorkman, Pamela J.
MetadataShow full item record
AbstractZn-alpha2-glycoprotein (ZAG) is a 41 kDa soluble protein that is present in most bodily fluids. The previously reported 2.8 A crystal structure of ZAG isolated from human serum demonstrated the structural similarity between ZAG and class I major histocompatibility complex (MHC) molecules and revealed a non-peptidic ligand in the ZAG counterpart of the MHC peptide-binding groove. Here we present crystallographic studies to explore further the nature of the non-peptidic ligand in the ZAG groove. Comparison of the structures of several forms of recombinant ZAG, including a 1.95 A structure derived from ZAG expressed in insect cells, suggests that the non-peptidic ligand in the current structures and in the structure of serum ZAG is a polyethylene glycol (PEG), which is present in the crystallization conditions used. Further support for PEG binding in the ZAG groove is provided by the finding that PEG displaces a fluorophore-tagged fatty acid from the ZAG binding site. From these results we hypothesize that our purified forms of ZAG do not contain a bound endogenous ligand, but that the ZAG groove is capable of binding hydrophobic molecules, which may relate to its function.
CitationDelker SL, West AP, McDermott L, Kennedy MW, Bjorkman PJ (2004) 'Crystallographic studies of ligand binding by Zn-alpha(2)-glycoprotein', Journal of Structural Biology, 148 (2), pp.205-213.
JournalJournal of Structural Biology
- Crystal structure of the novel complex formed between zinc alpha2-glycoprotein (ZAG) and prolactin-inducible protein (PIP) from human seminal plasma.
- Authors: Hassan MI, Bilgrami S, Kumar V, Singh N, Yadav S, Kaur P, Singh TP
- Issue date: 2008 Dec 19
- Zn-alpha2-glycoprotein, an MHC class I-related glycoprotein regulator of adipose tissues: modification or abrogation of ligand binding by site-directed mutagenesis.
- Authors: McDermott LC, Freel JA, West AP, Bjorkman PJ, Kennedy MW
- Issue date: 2006 Feb 21
- Crystal structure of zinc-α2-glycoprotein in complex with a fatty acid reveals multiple different modes of protein-lipid binding.
- Authors: Lau AM, Zahid H, Gor J, Perkins SJ, Coker AR, McDermott LC
- Issue date: 2019 Oct 15
- Strong and weak zinc binding sites in human zinc-α2-glycoprotein.
- Authors: Kumar AA, Hati D, Thaker TM, Miah L, Cunningham P, Domene C, Bui TT, Drake AF, McDermott LC
- Issue date: 2013 Dec 11
- Zinc-induced oligomerization of zinc α2 glycoprotein reveals multiple fatty acid-binding sites.
- Authors: Zahid H, Miah L, Lau AM, Brochard L, Hati D, Bui TT, Drake AF, Gor J, Perkins SJ, McDermott LC
- Issue date: 2016 Jan 1