25-30 August 2019
Henry Ford Building
Europe/Berlin timezone

Relaxing with IDPs: NMR analysis of dynamics and molecular interactions

25 Aug 2019, 16:45
Max Kade Auditorium (Henry Ford Building)

Max Kade Auditorium

Henry Ford Building

Prize lecture Biological applications Prize Lectures


Dr Peter Wright (Scripps Research)


Intrinsically disordered proteins (IDPs) are highly abundant in the human proteome and are strongly associated with numerous devastating diseases, including cancers, age-related neurodegenerative disorders, diabetes, cardiovascular and infectious diseases. IDPs mediate critical regulatory functions in the cell, including transcription, translation, the cell cycle, and numerous signal transduction events. The lack of stable globular structure confers numerous functional advantages on IDPs, allowing them to exert an exquisite level of control over cellular signaling processes, but poses a major challenge to which traditional structural biology approaches are poorly suited. Many regulatory IDPs contain multiple interaction motifs. The intermolecular interface between such IDPs and their targets is energetically heterogeneous and is characterized by both static and dynamic interactions that mediate crosstalk between signaling pathways and lead to unique allosteric switches. NMR has emerged as the primary tool for elucidation of the structural ensembles, dynamics, interactions, posttranslational modifications, and functional mechanisms of IDPs. Relaxation measurements are especially important for characterization of IDP complexes, providing novel insights into the dynamic processes that mediate binding, competition for a common target, and allostery. The applications of NMR to elucidate the role of IDPs in dynamic cellular signaling will be illustrated by reference to the mechanism of action of a unidirectional, hypersensitive allosteric switch that downregulates the hypoxic response by displacing the hypoxia inducible factor HIF-1α from the general transcriptional coactivators CBP (CREB binding protein) and p300.

Primary authors

Dr Peter Wright (Scripps Research) Prof. Jane Dyson

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