Conformation and Dynamics of Nonnative States of Proteins studied by NMR Spectroscopy

Wirmer, Julia; Schlörb, Christian; Schwalbe, Harald

doi:10.1002/9783527619498.ch21

Cited by 6 publications

(7 citation statements)

References 247 publications

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“…Disordered proteins attract increasing attention, due in part to the fact that intrinsic disorder is prevalent in the proteomes of higher order organisms (Ward et al 2004 ). In addition, it has been established that the disordered states of proteins are not mere featureless ‘random coils’, but are characterized by secondary structure propensities of the polypeptide backbone, sometimes augmented with specific local interactions between side chains (Dill and Shortle 1991 ; Mittag and Forman-Kay 2007 ; Shortle 1996 ; Wirmer et al 2005 ). High-resolution determination of residual structure in these inherently flexible molecules is therefore necessary (Bartlett and Radford 2009 ).…”

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confidence: 99%

“…High-resolution determination of residual structure in these inherently flexible molecules is therefore necessary (Bartlett and Radford 2009 ). NMR spectroscopy is undoubtedly the most appropriate technique to offer detailed insight into disordered states, being sensitive to the length and time scales characterizing the atomic structure (Bartlett and Radford 2009 ; Eliezer 2009 ; Mulder et al 2009 ; Wirmer et al 2005 ). In our analyses of intrinsically disordered proteins (IDPs) we have been interested in the measurement of scalar coupling constants to probe the local polypeptide backbone structure.…”

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confidence: 99%

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Comprehensive determination of 3JHNHα for unfolded proteins using 13C′-resolved spin-echo difference spectroscopy

2009

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An experiment is presented to determine 3 J HNHa coupling constants, with significant advantages for applications to unfolded proteins. The determination of coupling constants for the peptide chain using 1D 1 H, or 2D and 3D 1 H-15 N correlation spectroscopy is often hampered by extensive resonance overlap when dealing with flexible, disordered proteins. In the experiment detailed here, the overlap problem is largely circumvented by recording 1 H-13 C 0 correlation spectra, which demonstrate superior resolution for unfolded proteins. J-coupling constants are extracted from the peak intensities in a pair of 2D spin-echo difference experiments, affording rapid acquisition of the coupling data. In an application to the cytoplasmic domain of human neuroligin-3 (hNlg3cyt) data were obtained for 78 residues, compared to 54 coupling constants obtained from a 3D HNHA experiment. The coupling constants suggest that hNlg3cyt is intrinsically disordered, with little propensity for structure.

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Comprehensive determination of 3JHNHα for unfolded proteins using 13C′-resolved spin-echo difference spectroscopy

2009

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“…We mention here those by Shortle (31) , 39) , Bracken et al (4) , Chatterjee and coworkers (9) , Wirmer, Schl ö rb, and Schwalbe (36) , and Meier et al (23) . Several excellent reviews on the subject of NMR spectroscopy of unfolded proteins exist, mostly with the focus on unfolded natively folded proteins.…”

Section: Introduction and Scopementioning

confidence: 90%

Nuclear Magnetic Resonance Spectroscopy Applied to (Intrinsically) Disordered Proteins

Mulder¹,

Lundqvist

Scheek³

2010

Instrumental Analysis of Intrinsically Disordered Proteins

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3NMR spectroscopy is undoubtedly the most suitable tool for investigating the details of IDPs. Many parameters in NMR, such as chemical shifts, line widths, spin -spin multiplet patterns, relaxation rates, and residual dipolar couplings (RDCs), are atom specifi c and harbor information about the local conformations that polypeptide chains adopt, including record of their dynamic behavior. J J J J ω J J J J J 2 2 6 4 0 3 J J

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“…Here, Ace is the N-acetyl group, Nme is the N′-methylamide group, and Xaa is the amino acid of interest. Nuclear magnetic resonance (NMR) experiments report scalar coupling constants that depend on the dihedral angle distribution of the given structural ensemble, 14 while data from infrared and Raman spectroscopy can be used to extract relative populations of distinct conformational classes. 15 Far ultraviolet spectra from circular dichroism measurements also have been used to determine relative populations of different conformations.…”

Section: Introductionmentioning

confidence: 99%

Experimentally Derived and Computationally Optimized Backbone Conformational Statistics for Blocked Amino Acids

Choi

Pappu

2018

J. Chem. Theory Comput.

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Experimentally derived, amino acid specific backbone dihedral angle distributions are invaluable for modeling data-driven conformational equilibria of proteins and for enabling quantitative assessments of the accuracies of molecular mechanics force fields. The protein coil library that is extracted from analysis of high-resolution structures of proteins has served as a useful proxy for quantifying intrinsic and context-dependent conformational distributions of amino acids. However, data that go into coil libraries will have hidden biases, and ad hoc procedures must be used to remove these biases. Here, we combine high-resolution biased information from protein structural databases with unbiased low-resolution information from spectroscopic measurements of blocked amino acids to obtain experimentally derived and computationally optimized coil-library landscapes for each of the 20 naturally occurring amino acids. Quantitative descriptions of conformational distributions require parsing of data into conformational basins with defined envelopes, centers, and statistical weights. We develop and deploy a numerical method to extract conformational basins. The weights of conformational basins are optimized to reproduce quantitative inferences drawn from spectroscopic experiments for blocked amino acids. The optimized distributions serve as touchstones for assessments of intrinsic conformational preferences and for quantitative comparisons of molecular mechanics force fields.

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Conformation and Dynamics of Nonnative States of Proteins studied by NMR Spectroscopy

Cited by 6 publications

References 247 publications

Comprehensive determination of 3JHNHα for unfolded proteins using 13C′-resolved spin-echo difference spectroscopy

Comprehensive determination of 3JHNHα for unfolded proteins using 13C′-resolved spin-echo difference spectroscopy

Nuclear Magnetic Resonance Spectroscopy Applied to (Intrinsically) Disordered Proteins

Experimentally Derived and Computationally Optimized Backbone Conformational Statistics for Blocked Amino Acids

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