New insights into the zinc-α2-glycoprotein (ZAG) scaffold and its metal ions binding abilities using spectroscopic techniques

Life Sci. 2020 May 15:249:117462. doi: 10.1016/j.lfs.2020.117462. Epub 2020 Feb 22.

Abstract

Aims: Zinc-α2-glycoprotein (ZAG) is soluble lipid mobilizing protein and a noval adipokine associated with cancer cachexia. ZAG is an omnipresent protein and represent a fold of MHC class I proteins. Although ZAG's metal binding capacity has already been reported, no other metal has been mapped to date besides the complex formation with zinc.

Main methodology: In this study, fluorescence emission spectroscopy and mass spectrometry (MALDI-TOF) were employed to define the putative interaction sites and their accessibility for the biologically important metals of Irving William Series.

Key findings: Several hotspot residues in the ZAG scaffold involved in these interactions were mapped and their binding affinity score for each metal has been determined. Thebinding abilities of these sites and aggregation propensities of ZAG were monitored by fluorescence emission spectroscopy.

Significance: The prediction of such binding affinity with metals on the active sites and its impact on the conformational states to accelerate aggregation was discussed as an important finding that may be involved in several other biochemical processes such as lipid binding, β-adrenergic receptors, cancer cachexia and association with plasma cholesterol and obesity.

Keywords: Fluorescence emission spectroscopy; Irving Williams Series metals; MALDI TOF; MHC-1 scaffold; Zn-α(2)-glycoprotein.

MeSH terms

  • Binding Sites
  • Protein Binding
  • Seminal Plasma Proteins / metabolism*
  • Spectrometry, Fluorescence / methods
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Zinc / metabolism*
  • Zn-Alpha-2-Glycoprotein

Substances

  • Seminal Plasma Proteins
  • Zn-Alpha-2-Glycoprotein
  • Zinc