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Defining the Interaction of Human Soluble Lectin ZG16p and Mycobacterial Phosphatidylinositol Mannosides
Shinya Hanashima1, Sebastian Götze2,3, Yan Liu4
1Structural Glycobiology Team, RIKEN-Max Planck Joint Research Center for Systems Chemical Biology, RIKEN Global Research Cluster, Wako, Saitama 351-0198 (Japan).
Abstract:
ZG16p is a soluble mammalian lectin that interacts with mannose and heparan sulfate. Here we describe detailed analysis of the interaction of human ZG16p with mycobacterial phosphatidylinositol mannosides (PIMs) by glycan microarray and NMR. Pathogen-related glycan microarray analysis identified phosphatidylinositol mono- and di-mannosides (PIM1 and PIM2) as novel ligand candidates of ZG16p. Saturation transfer difference (STD) NMR and transferred NOE experiments with chemically synthesized PIM glycans indicate that PIMs preferentially interact with ZG16p by using the mannose residues. The binding site of PIM was identified by chemical-shift perturbation experiments with uniformly (15)N-labeled ZG16p. NMR results with docking simulations suggest a binding mode of ZG16p and PIM glycan; this will help to elucidate the physiological role of ZG16p.
Insights
Human ZG16p lectin binds to mycobacterial phosphatidylinositol mannosides (PIMs), specifically PIM1 and PIM2. This interaction, mediated by mannose residues, sheds light on ZG16p's function in pathogen recognition.
Area of Science:
- Biochemistry
- Immunology
- Glycobiology
Background:
- ZG16p is a soluble mammalian lectin known to bind mannose and heparan sulfate.
- Understanding ZG16p's interactions with microbial components is crucial for elucidating its role in host-pathogen responses.
Purpose of the Study:
- To investigate the interaction between human ZG16p and mycobacterial phosphatidylinositol mannosides (PIMs).
- To identify specific PIM structures recognized by ZG16p and characterize the binding site and mode.
Main Methods:
- Glycan microarray analysis to identify potential PIM ligands for ZG16p.
- Nuclear Magnetic Resonance (NMR) spectroscopy, including Saturation Transfer Difference (STD) NMR and transferred NOE, to study binding.
- Chemical-shift perturbation experiments using (15)N-labeled ZG16p to map the binding site.
- Molecular docking simulations to predict the binding mode.
Main Results:
- Pathogen-related glycan microarray identified phosphatidylinositol mono- (PIM1) and di-mannosides (PIM2) as novel ZG16p ligand candidates.
- NMR studies demonstrated that ZG16p preferentially interacts with PIMs via their mannose residues.
- Chemical-shift perturbation mapped the PIM glycan binding site on ZG16p.
- NMR data combined with docking simulations proposed a specific binding mode.
Conclusions:
- Human ZG16p recognizes and binds to specific mycobacterial PIM glycans (PIM1 and PIM2).
- The interaction is primarily mediated through the mannose moieties of the PIMs.
- The characterized binding site and mode provide a foundation for understanding ZG16p's physiological role in immunity and host-pathogen interactions.
