Related ArticlesNMR Detection of Semi-Specific Antibody Interactions in Serum Environments.
Molecules. 2017 Sep 27;22(10):
Authors: Yanaka S, Yamazaki T, Yogo R, Noda M, Uchiyama S, Yagi H, Kato K
Abstract
Although antibody functions are executed in heterogeneous blood streams characterized by molecular crowding and promiscuous intermolecular interaction, detailed structural characterizations of antibody interactions have thus far been performed under homogeneous in vitro conditions. NMR spectroscopy potentially has the ability to study protein structures in heterogeneous environments, assuming that the target protein can be labeled with NMR-active isotopes. Based on our successful development of isotope labeling of antibody glycoproteins, here we apply NMR spectroscopy to characterize antibody interactions in heterogeneous extracellular environments using mouse IgG-Fc as a test molecule. In human serum, many of the HSQC peaks originating from the Fc backbone exhibited attenuation in intensity of various magnitudes. Similar spectral changes were induced by the Fab fragment of polyclonal IgG isolated from the serum, but not by serum albumin, indicating that a subset of antibodies reactive with mouse IgG-Fc exists in human serum without preimmunization. The metaepitopes recognized by serum polyclonal IgG cover the entire molecular surface of Fc, including the binding sites to Fc receptors and C1q. In-serum NMR observation will offer useful tools for the detailed characterization of biopharamaceuticals, including therapeutic antibodies in physiologically relevant heterogeneous environments, also giving deeper insight into molecular recognition by polyclonal antibodies in the immune system.
[NMR paper] Domain-specific interactions between MLN8237 and human serum albumin estimated by STD and WaterLOGSY NMR, ITC, spectroscopic, and docking techniques.
Domain-specific interactions between MLN8237 and human serum albumin estimated by STD and WaterLOGSY NMR, ITC, spectroscopic, and docking techniques.
Related Articles Domain-specific interactions between MLN8237 and human serum albumin estimated by STD and WaterLOGSY NMR, ITC, spectroscopic, and docking techniques.
Sci Rep. 2017 Mar 30;7:45514
Authors: Yang H, Liu J, Huang Y, Gao R, Tang B, Li S, He J, Li H
Abstract
Alisertib (MLN8237) is an orally administered inhibitor of Aurora A kinase. This small-molecule inhibitor is under...
nmrlearner
Journal club
0
03-31-2017 12:43 PM
[NMR paper] Target-specific NMR detection of protein-ligand interactions with antibody-relayed (15)N-group selective STD.
Target-specific NMR detection of protein-ligand interactions with antibody-relayed (15)N-group selective STD.
Target-specific NMR detection of protein-ligand interactions with antibody-relayed (15)N-group selective STD.
J Biomol NMR. 2016 Nov 24;
Authors: Hetényi A, Heged?s Z, Fajka-Boja R, Monostori É, Kövér KE, Martinek TA
Abstract
Fragment-based drug design has been successfully applied to challenging targets where the detection of the weak protein-ligand interactions is a key element. (1)H saturation transfer difference...
nmrlearner
Journal club
0
11-26-2016 12:27 PM
Target-specific NMR detection of proteinâ??ligand interactions with antibody-relayed 15 N-group selective STD
Target-specific NMR detection of proteinâ??ligand interactions with antibody-relayed 15 N-group selective STD
Abstract
Fragment-based drug design has been successfully applied to challenging targets where the detection of the weak proteinâ??ligand interactions is a key element. 1H saturation transfer difference (STD) NMR spectroscopy is a powerful technique for this work but it requires pure homogeneous proteins as targets. Monoclonal antibody (mAb)-relayed 15N-GS STD spectroscopy has been developed to resolve the problem of protein mixtures and...
nmrlearner
Journal club
0
11-25-2016 02:22 AM
Exploring weak, transient protein-protein interactions in crowded in vivo environments by in-cell NMR spectroscopy.
Exploring weak, transient protein-protein interactions in crowded in vivo environments by in-cell NMR spectroscopy.
Exploring weak, transient protein-protein interactions in crowded in vivo environments by in-cell NMR spectroscopy.
Biochemistry. 2011 Sep 26;
Authors: Wang Q, Zhuravleva A, Gierasch LM
Abstract
Biology relies on functional interplay of proteins in the crowded and heterogeneous environment inside cells, and functional protein interactions are often weak and transient. Thus, methods are needed that preserve these...
nmrlearner
Journal club
0
09-30-2011 05:59 AM
A Solution NMR Study of the Interactions of Oligomannosides and the Anti-HIV-1 2G12 Antibody Reveals Distinct Binding Modes for Branched Ligands*
A Solution NMR Study of the Interactions of Oligomannosides and the Anti-HIV-1 2G12 Antibody Reveals Distinct Binding Modes for Branched Ligands*
A Solution NMR Study of the Interactions of Oligomannosides and the Anti-HIV-1 2G12 Antibody Reveals Distinct Binding Modes for Branched Ligands*
Chemistry. 2011 Feb 1;17(5):1547-1560
Authors: Enríquez-Navas PM, Marradi M, Padro D, Angulo J, Penadés S
The structural and affinity details of the interactions of synthetic oligomannosides, linear (di-, tri-, and tetra-) and branched (penta- and hepta-),...
nmrlearner
Journal club
0
01-27-2011 02:52 PM
A Solution NMR Study of the Interactions of Oligomannosides and the Anti-HIV-1 2G12 Antibody Reveals Distinct Binding Modes for Branched Ligands*
A Solution NMR Study of the Interactions of Oligomannosides and the Anti-HIV-1 2G12 Antibody Reveals Distinct Binding Modes for Branched Ligands*
A Solution NMR Study of the Interactions of Oligomannosides and the Anti-HIV-1 2G12 Antibody Reveals Distinct Binding Modes for Branched Ligands*
Chemistry. 2011 Jan 5;
Authors: Enríquez-Navas PM, Marradi M, Padro D, Angulo J, Penadés S
The structural and affinity details of the interactions of synthetic oligomannosides, linear (di-, tri-, and tetra-) and branched (penta- and hepta-), with the broadly...
nmrlearner
Journal club
0
01-06-2011 11:21 AM
[NMR paper] Specific in vitro labeling of cells with a fluorine-19 probe encapsulated in antibody
Specific in vitro labeling of cells with a fluorine-19 probe encapsulated in antibody-targeted liposomes: a F-19 NMR spectroscopy study.
Related Articles Specific in vitro labeling of cells with a fluorine-19 probe encapsulated in antibody-targeted liposomes: a F-19 NMR spectroscopy study.
Magn Reson Med. 1993 Feb;29(2):252-5
Authors: Vion-Dury J, Machy P, Confort-Gouny S, Leserman L, Cozzone PJ
Liposomes containing dexamethasone phosphate (DMp) were covalently coupled to protein A and then incubated with murine L929 fibroblast and RDM4...
nmrlearner
Journal club
0
08-21-2010 11:53 PM
Detection of unrealistic molecular environments in protein structures based on expect
Abstract Understanding the relationship between protein structure and biological function is a central theme in structural biology. Advances are severely hampered by errors in experimentally determined protein structures. Detection and correction of such errors is therefore of utmost importance. Electron densities in molecular structures obey certain rules which depend on the molecular environment. Here we present and discuss a new approach that relates electron densities computed from a structural model to densities expected from prior observations on identical or closely related molecular...