Informace o publikaci

NMR as a tool for studies of (partially) disordered proteins and their interactions

Název česky NMR jako nástroj pro studium (částečně) neuspořádaných proteinů a jejich interakcí


Rok publikování 2010
Druh Konferenční abstrakty
Fakulta / Pracoviště MU

Přírodovědecká fakulta

Popis One third of eukaryotic proteins, including human, contains disordered regions longer than 30 amino acids. The intrinsically disordered proteins have well-defined biological functions, some of them may adopt a regular structure on binding to their interacting partners, and many of them are related to human diseases. The lack of a unique structure makes the disordered proteins poor targets for crystallographic studies. Therefore, nuclear magnetic resonance (NMR) plays a crucial role in studies of disordered proteins. NMR can provide valuable information on residual secondary structure, possible long-range contacts, internal dynamics of the disordered polypeptide chain, and its structuring upon interactions with other proteins. The first step in NMR investigation of a disordered protein and its interactions is the assignment of observed spectral frequencies to individual atoms in the polypeptide chain. Combination of the structural disorder with a high incidence of sequential repeats often results in spectra with severely overlapped peaks, impossible to assign by the traditional approach. A novel assignment strategy, based on NMR experiments with extreme resolution will be presented. Two examples of partially disordered proteins, involved in protein-protein and/or protein-DNA interactions will be discussed: Retroviral protease of the murine intracisternal A-type particle (assigned by the traditional approach) and delta subunit of RNA polymerase from Bacillus subtillis (assigned by the novel strategy). Results of studies of both proteins interacting with their molecular partners will be presented. The retroviral protease, studied by NMR titration experiment, represents an example of interactions of two unstructured molecules, a disordered protein domain and ss-DNA oligonucleotide. The interactions of the RNA polymerase subunit were studied by gel-shift assay and the interaction surface of the protein, structure of which was determined within the project, was identified by evolutionary analysis. Analysis of internal motions of the subunit, based on NMR relaxation dispersion measurements, showed a strong correlation between conformational changes and intermolecular contacts.
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