Session FOA. There are 5 abstracts in this session.

Session: Disorder in Proteins, time: 08:30-8:55
Deciphering the Dynamic Interaction Profile of an Intrinsically Disordered Protein using Exchange Spectroscopy
Elise Delaforge1; Jaka Kragelj1; Laura Tengo1; Andrés Palencia2; Sigrid Milles1; Guillaume Bouvignies3; Nicola Salvi1; Martin Blackledge1; Malene R. Jensen1
1Institut de Biologie Structurale, Grenoble, France; 2Institute for Advanced Biosciences, Grenoble, France; 3Ecole Normale Superieur (ENS), Paris, France
Intrinsically disordered proteins (IDPs) can display different interaction modes including folding-upon-binding or binding through dynamic, so-called fuzzy, complexes. The majority of information about binding modes has been inferred from crystal structures of proteins in complex with peptides of IDPs. However, crystal structures provide a mainly static view of the complexes and do not give information about the dynamics of the IDP in the bound state. We combine CPMG relaxation dispersion and CEST to decipher the interaction profile of an IDP in complex with its partner. We study the signaling complex between p38α and the disordered regulatory domain of MKK4. We demonstrate that MKK4 employs a combination of interaction modes leading to a complex displaying different dynamics across the bound regions.

Session: Disorder in Proteins, time: 08:55-9:20
High dimensionality and high resolution NMR experiments for Intrinsically disordered proteins 
Wiktor Kozminski
University of Warsaw, Warsaw, Poland
A variety of different methods based on non-uniform sampling were proposed to overcome sampling limitation in multidimensional NMR spectroscopy. They could be utilized in two different ways, either to shorten the experiment duration without loss of resolution, or to perform experiments that are not obtainable conventionally, i.e. with high number of dimensions and high resolution. Its full potential is manifested when the overall experiment time is less important than a new information available from 5-7 D NMR spectra. The new methods are applied for NMR studies of intrinsically disordered proteins, where the structural disorder in combination with highly repetitive amino-acid sequences causes severe peak overlap in the spectra.

Session: Disorder in Proteins, time: 09:20-9:45
NMR spectroscopy Unravels Molecular Transitions in the Alzheimer-related IDP Tau
Markus Zweckstetter1, 2
1German Center for Neurodegenerative Diseases, Göttingen, Germany; 2Max Planck Institute for Biophysical Chemistry, Göttingen, Germany
The intrinsically disordered protein Tau plays a critical role in Alzheimer’s disease. Many efforts have been made over the years to understand Tau structure as a way to understand Tau function and its mechanisms of physiological and toxic action, but these efforts have primarily used traditional biochemistry and molecular biology approaches and therefore have addressed structure and function at a relatively primitive level. We use NMR spectroscopy to understand the structure and dynamics of Tau and its physiological and pathogenic interactions. In the presentation, I will highlight the NMR tools, which provide unique insight into the role of disorder for molecular transitions in Tau.

Session: Disorder in Proteins, time: 09:45-10:00

Conformational ensemble of disordered proteins probed by NMR solvent Paramagnetic Relaxation Enhancements (sPRE)

Hamed Kooshapur; Charles Schwieters; Nico Tjandra
National Institutes of Health, Bethesda, MD

Intrinsically disordered proteins (IDPs) play significant roles in many biological processes and have been implicated in several diseases such as Alzheimer’s and Parkinson. Characterization of the conformational ensemble of IDPs is highly important but remains a challenge due to the astronomical degrees of freedom that they can adopt and insufficient number of observables. NMR is very powerful in this regard and several types of NMR data, such as residual dipolar couplings (RDCs) and paramagnetic relaxation enhancements (PREs), have been used in studying IDPs. Here, we show that PREs obtained from a soluble paramagnetic probe, known as solvent PRE (sPRE), provide unique information that can be used in combination with other NMR data to define the conformational ensemble of disordered proteins.

Session: Disorder in Proteins, time: 10:00-10:15
Molecular Recognition of Globular and Intrinsically Disordered protein from High-Power Relaxation Dispersion Measurements 
Supriya Pratihar1; Kalyan Chakrabarti1; G Jithender Reddy1; Stefan Becker1; Bert de Groot1; Donghan Lee2; Thomas Weikl3; Christian Griesinger1
1Max Planck Institute for Biophysical Chemistry, Gottingen, Germany; 2University of Louisville, Louisville, KY; 3Max Planck Institute for Colloids and Interfaces, Potsdam, Germany
Protein dynamics is crucial for its function. Recently by applying 40 kHz power on 1H we could detect a functionally relevant global motion in GB3. In a solenoid coil it is possible to apply 300 KHz power which can detect even 300 ns motion. Using the high-power RD method we have characterized the fast folding kinetics in p53, which adopts an α-helix (aa18-26) with a population of 30% in the wt and 60% in a P27A mutant. Surprisingly, the folding process slowed down on average 80-fold in the P27A mutant. High power RD method along with a theoretical model is currently being employed to investigate the binding kinetics and by that the binding mechanism of ubiquitin with SH3.