Creative BioMart provides analytical services for peptide-MHC and protein nuclear magnetic resonance spectroscopy (BioNMR) for structure determination and fragment screening of MHC complexes.

BioNMR and Exploration of the Conformational Dynamics of MHC

Nuclear magnetic resonance spectroscopy (NMR) is one of the main experimental techniques used in structural biology to determine atomic-resolution structures and study the dynamic characteristics and intermolecular interactions of biological macromolecules. The most important aspect of structural analysis of peptide or protein NMR spectra is the assignment of peaks detected in the NMR spectrum to individual atoms (assignment of detected peaks to individual atoms). This is done based on various research needs such as peptide primary structure determination, protein secondary structure assessment, 2D 15N NMR spectral assignment for epitope mapping, fragment screening, and Kd determination. In addition, doing so provides information on whether the structure of a peptide or protein can be determined. If proteins can be assigned, BioNMR can be applied for structural analysis of protein complexes, and de novo structure determination of complexes is possible even if the structures of the components are unknown.

Fig.1 Superimposition of crystal and modeled structures of major histocompatibility complex (MHC) molecules. (Yanaka S, et al. 2017)

Technical Features

MHC molecules are loaded with a variety of self and non-self peptides in their binding grooves. The crystal structures of a large number of different MHC alleles with different binding peptides have been determined and found to be very similar to each other, regardless of how the binding peptides are sequenced. The conformational dynamics of MHC molecules may affect MHC stability differences, and the conformational dynamics of MHC molecules may affect peptide loading and presentation. NMR can be applied to the resolution of MHC peptide complexes.

Our BioNMR Service

BioNMR is a powerful and versatile technique that provides detailed structures of macromolecules and information on how they interact with their ligands. The full and detailed 3D structures of proteins and protein-ligand complexes can be determined using BioNMR, a feature that has potential applications in the drug discovery and design stages. Our services are based on NMR techniques to obtain information about the structure of peptides, proteins and their complexes through nuclear magnetic resonance spectroscopy. NMR is a gold standard technique for validating the binding of hits and mapping their binding sites. At the same time, it can be used to screen multiple protein targets for rapid analysis simultaneously. This service is for biotherapeutic protein/antibody drug discovery, and our BioNMR testing service can be used as a screening assay, as well as for fragments that are expected to bind weakly.

Applications of BioNMR

• Routine NMR testing service
• Structural elucidation by NMR
• Characterization and interaction analysis by NMR

Fig.2 Featured peptide-MHC complex BioNMR service.

Please contact us if you need more information, a quote or to schedule a conference call.

References

• Yanaka S, Sugase K. Exploration of the conformational dynamics of major histocompatibility complex molecules[J]. Frontiers in Immunology, 2017, 8: 632.
• Yanaka S, Ueno T, Shi Y, et al. Peptide-dependent conformational fluctuation determines the stability of the human leukocyte antigen class I complex[J]. Journal of Biological Chemistry, 2014, 289(35): 24680-24690.