NMR spectroscopy is the only experimental technique with abilities to determine atomic resolution structures as well as to investigate intermolecular interactions of biological macromolecules and their dynamics over a range of different time scales at atomic detail. These unique characteristics of NMR spectroscopy allow the investigation of important biological events that are relatively inaccessible to other techniques. In the current view, almost all proteins are believed to populate partially folded species, so called folding intermediates, along their way to the native state. These folding intermediates play a key role in defining protein folding and assembly pathways as well as those of misfolding and aggregation. Structural characterization of the folding pathway and in addition of the intermediate state of the antibody domain CL by NMR spectroscopy provides insights into minor structural differences in an intermediate that can shape the folding landscape decisively to favor either folding or misfolding. Although many proteins fold to their native structures rapidly and spontaneously, recent studies indicate that a surprisingly high number of gene sequences in eukaryotic genomes encode intrinsically disordered proteins. NMR spectroscopic investigation on the structural characteristics of the CH1 domain of the antibody molecule extends the growing class of unfolded proteins by a prominent member of the immunoglobulin superfamily. Only upon association with the antibody light chain, the interaction with the CL domain induces structure formation in the CH1 domain. A detailed description of this induced folding reveals insights into the mechanism of folding upon binding by which intrinsically disordered proteins perform their diverse biological functions like in the case of antibody molecules the secretion control from the ER. In contrast, intrinsically structured proteins must exhibit a distinct mechanism to fulfill their biological functions and transfer cellular signals. Instead of inducing folding, binding of a ligand induces conformational changes. NMR spectroscopic investigation of the pH sensitive module of the focal adhesion associated protein talin indicates a structural mechanism for pH dependent actin binding, suggesting an allosteric regulation in the process of cell migration.      «

NMR spectroscopy is the only experimental technique with abilities to determine atomic resolution structures as well as to investigate intermolecular interactions of biological macromolecules and their dynamics over a range of different time scales at atomic detail. These unique characteristics of NMR spectroscopy allow the investigation of important biological events that are relatively inaccessible to other techniques. In the current view, almost all proteins are believed to populate partiall...     »

Die NMR Spektroskopie stellt nach wie vor die einzige Methode dar, mittels der sich dynamische Vorgänge von Proteinen auf atomarer Ebene und über eine beachtliche Zeitskala untersuchen lassen. Dies ermöglicht unter anderem einen Einblick in die Proteinfaltung oder auch in grundlegende zelluläre Prozesse. Untersuchungen des Faltungsweges der Antikörperdomänen CL und CH1 identifizierten zum einen strukturelle Elemente, die CL zur nativen Faltung verhelfen und Missfaltung vermeiden und zeigten zum anderen die biologische Relevanz eines intrinsisch ungefalteten Proteins. Des weiteren konnte ein Einblick in die allosterische Kommunikation innerhalb des Proteins Talin gegeben werden, das den Prozess der Zellmigration entscheidend beeinflusst.     «

Die NMR Spektroskopie stellt nach wie vor die einzige Methode dar, mittels der sich dynamische Vorgänge von Proteinen auf atomarer Ebene und über eine beachtliche Zeitskala untersuchen lassen. Dies ermöglicht unter anderem einen Einblick in die Proteinfaltung oder auch in grundlegende zelluläre Prozesse. Untersuchungen des Faltungsweges der Antikörperdomänen CL und CH1 identifizierten zum einen strukturelle Elemente, die CL zur nativen Faltung verhelfen und Missfaltung vermeiden und zeigten zum...     »