RESUMO
A novel statistical analysis of paramagnetic relaxation enhancement (PRE) and paramagnetic relaxation interference (PRI) based nuclear magnetic resonance (NMR) data is proposed based on the computation of correlation matrices. The technique is demonstrated with an example of the intrinsically disordered proteins (IDPs) osteopontin (OPN) and brain acid soluble protein 1 (BASP1). The correlation analysis visualizes in detail the subtleties of conformational averaging in IDPs and highlights the presence of correlated structural fluctuations of individual sub-domains in IDPs.
Assuntos
Proteínas Intrinsicamente Desordenadas/química , Ressonância Magnética Nuclear Biomolecular , Humanos , Proteínas Intrinsicamente Desordenadas/metabolismo , Proteínas de Membrana/química , Proteínas de Membrana/metabolismo , Modelos Moleculares , Proteínas do Tecido Nervoso/química , Proteínas do Tecido Nervoso/metabolismo , Osteopontina/química , Osteopontina/metabolismo , Estrutura Terciária de Proteína , Proteínas Repressoras/química , Proteínas Repressoras/metabolismoRESUMO
Hyperpolarized water can selectively enhance NMR signals of rapidly exchanging protons in osteopontin (OPN), a metastasis-associated intrinsically disordered protein (IDP), at near-physiological pH and temperature. The transfer of magnetization from hyperpolarized water is limited to solvent-exposed residues and therefore selectively enhances signals in 1 H-15 N correlation spectra. Binding to the polysaccharide heparin was found to induce the unfolding of preformed structural elements in OPN.
Assuntos
Ressonância Magnética Nuclear Biomolecular , Osteopontina/química , Polissacarídeos/química , Água/química , Concentração de Íons de Hidrogênio , Prótons , Solventes/química , TemperaturaRESUMO
A graph theoretical analysis of nuclear magnetic resonance (NMR) data of six different protein interactions has been presented. The representation of the protein interaction data as a graph or network reveals that all of the studied interactions are based on a common functional concept. They all involve a single densely packed hub of functionally correlated residues that mediate the ligand binding events. This is found independent of the kind of protein (folded or unfolded) or ligand (protein, polymer or small molecule). Furthermore, the power of the graph analysis is demonstrated at the examples of the Calmodulin (CaM)/Calcium and the Cold Shock Protein A (CspA)/RNA interaction. The presented approach enables the precise determination of multiple binding sites for the respective ligand molecules.