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

Dynamic Complexes and Complex Dynamics - NMR Studies of Large Scale Protein Motions

30 Aug 2019, 14:50
Max Kade Auditorium (Henry Ford Building)

Max Kade Auditorium

Henry Ford Building

Plenary talk Dynamics Plenary Lectures


Dr Martin Blackledge (Protein Dynamics and Flexibility by NMR)


Proteins are inherently dynamic, exhibiting conformational freedom on many timescales,1 implicating structural rearrangements that play a major role in molecular interaction, thermodynamic stability and biological function. Intrinsically disordered proteins (IDPs) represent extreme examples where flexibility defines molecular function. IDPs exhibit highly heterogeneous local and long-range structural and dynamic propensities, sampling a much flatter energy landscape than their folded counterparts, allowing inter-conversion between a quasi-continuum of accessible conformations.2 We are combining multifield NMR relaxation measurements and ensemble MD approaches to develop a unified description of the dynamics of IDPs as a function of environmental conditions.3-5
In spite of the ubiquitous presence of IDPs throughout biology, the molecular mechanisms regulating their interactions with physiological partners remain poorly understood. We use NMR spectroscopy to map these complex molecular recognition trajectories at atomic resolution, from the highly dynamic free-state equilibrium to the bound state ensemble. Examples include the replication machinery of Measles virus, where the highly (>70%) disordered phosphoprotein initiates transcription and replication exploiting weak interactions with ordered and disordered domains of the nucleoprotein,6,7 the nuclear pore, where weak interactions between the nuclear transporter and highly flexible chains containing multiple ultra-short recognition motifs, facilitate fast passage into the nucleus.8 and large-scale domain dynamics in Influenza H5N1 polymerase are essential for import into the nucleus of the infected cell.9
[1]. Lewandowski et al Science 348, 578 (2015)
[2]. Jensen et al Chem Rev 114, 6632 (2014)
[3]. Abyzov et al J.A.C.S. 138, 6240 (2016)
[4]. Salvi et al Angew Chem Int Ed. 56, 14020 (2017)
[5]. Salvi et al Science Advances In Press (2019)
[6]. Schneider et al J.A.C.S. 137,1220 (2015)
[8]. Milles et al Science Advances 163, 734 (2018)
[8]. Milles et al Cell 112, 3409 (2015)
[9]. Delaforge et al J.A.C.S. 137 (2015)

Primary author

Dr Martin Blackledge (Protein Dynamics and Flexibility by NMR)

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