Abstracts
FEBS National Lecturer Award:
NMR Provides Unprecedented Insight into the Role of Intrinsically Disordered Proteins in the Replication of Pathogenic RNA Viruses
Martin Blackledge
Protein Dynamics and Flexibility by NMR, Institut de Biologie Structurale (IBS), UGA-CEA-CNRS, 71 Avenue des Martyrs, 38000 Grenoble, France, martin.blackledge@ibs.fr
Authors: Martin Blackledge, Aldo Camacho-Zarco, Serafima Guseva, Lefan Yu, Yi-Hsin Chen, Sigrid Milles, Maiia Botova, Luiza Bessa, Vincent Schnapka
Proteins are inherently dynamic, exhibiting conformational freedom on many timescales, implicating structural rearrangements that play a major role in molecular interaction. Intrinsically disordered proteins (IDPs) represent extreme examples where flexibility defines function. We use NMR spectroscopy to develop a unified description of the dynamics of IDPs as a function of environmental conditions, from membraneless organelles to in-cell,1-3 and to map complex molecular recognition trajectories at atomic resolution.4 Examples include the replication machinery of Measles virus, where we use NMR to characterize the 92 kDa complex formed between the highly disordered phosphoprotein and the nucleoprotein prior to nucleocapsid assembly – a process that we can also follow in real-time.5,6 These proteins undergo liquid-liquid phase separation upon mixing and we can use NMR to describe the molecular basis and functional advantages of this phenomenon.7 NMR also sheds new light on the molecular basis of host adaptation of influenza polymerase, via a highly dynamic multivalent interaction,8,9 and reveals the dynamic assembly of SARS-CoV-2 nucleoprotein with its viral partner nsp3,10 and the role of hyperphosphorylation in the viral cycle.11
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