Functional protein dynamics on uncharted time scales detected by nanoparticle-assisted NMR spin relaxation

Xie, Mouzhe; Yu, Lei; Bruschweiler‐Li, Lei; Xiang, Xinyao; Hansen, Alexandar L.; Brüschweiler, Rafael

doi:10.1126/sciadv.aax5560

Cited by 35 publications

(58 citation statements)

References 66 publications

(79 reference statements)

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“…Due to the pronounced flexibility in IDPs 15 N spin relaxation is typically dominated by local fluctuations on different timescales rather than the global tumbling of the protein [58][59][60][61][62]. In a fully extended conformation 15 N transverse relaxation is dominated by fast time scale motions around the C α -C α direction [58,59,[63][64][65], as described by the (GAF) Gaussian Axial Fluctuation model [66]. Bending of the polypeptide chain due to formation of the cis-form may restrict this dynamic mode and increase the effective local correlation time which would be accompanied by faster 15 N-R 2 relaxation.…”

Section: The Structural Dynamics Of Cis Formsmentioning

confidence: 99%

The Ambivalent Role of Proline Residues in an Intrinsically Disordered Protein: From Disorder Promoters to Compaction Facilitators

Mateos

Conrad-Billroth

Schiavina

et al. 2020

Journal of Molecular Biology

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Intrinsically disordered proteins (IDPs) carry out many biological functions. They lack a stable three-dimensional structure, but rather adopt many different conformations in dynamic equilibrium. The interplay between local dynamics and global rearrangements is key for their function. In IDPs, proline residues are significantly enriched. Given their unique physicochemical and structural properties, a more detailed understanding of their potential role in stabilizing partially folded states in IDPs is highly desirable. Nuclear magnetic resonance (NMR) spectroscopy, and in particular 13 C-detected NMR, is especially suitable to address these questions. We applied a 13 C-detected strategy to study Osteopontin, a largely disordered IDP with a central compact region. By employing the exquisite sensitivity and spectral resolution of these novel techniques we gained unprecedented insight into cis-Pro populations, their local structural dynamics and their role in mediating long-range contacts. Our findings clearly call for a reassessment of the structural and functional role of proline residues in IDPs. The emerging picture shows that proline residues have ambivalent structural roles. They are not simply disorder promoters but rather can, depending on the primary sequence context, act as nucleation sites for structural compaction in IDPs. These unexpected features provide a versatile mechanistic toolbox to enrich the conformational ensembles of IDPs with specific features for adapting to changing molecular and cellular environments.

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Section: The Structural Dynamics Of Cis Formsmentioning

confidence: 99%

The Ambivalent Role of Proline Residues in an Intrinsically Disordered Protein: From Disorder Promoters to Compaction Facilitators

Mateos

Conrad-Billroth

Schiavina

et al. 2020

Journal of Molecular Biology

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“…The nature and functional role of these motions should be clarified to carry out NMR experiments exquisitely sensitive to these motions. Studying proteins in the presence of nanoparticles is a significant progress in understanding the details of this protein dynamics (Xie et al 2019). This approach showed large-scale dynamics of loops that are involved in functionally critical protein-protein interactions and protein-calcium ion recognition.…”

Section: Magnetic Resonance Studying Water In Polymers Natural Biomamentioning

confidence: 99%

“…The interactions between water and biomolecules were investigated by NMR methods for a long period of time (Kuntz et al 1969;Wüthrich et al 1996;Krishman 1996;Wider 1998;Szuminska et al 2001;Van-Quynh et al 2003;Cosgrove et al 2007;Rodin et al 2014Rodin et al , 2017Belton 2011;Foster et al 2016;Mandala et al 2018;Yazawa et al 2016;Zubow et al 2016;Kerch 2018;Callaghan and Lelievre 1986). The data obtained discovered hydration features and resulted in the development of the hydration models (Kuntz et al 1969;Kuntz and Kauzmann 1974;Mathur-De Vre 1979;Wüthrich et al 1996;Otting 1997;Halle 2004;Cosgrove et al 2007;Belton 2011;Xie et al 2019). The NMR methods studied also frozen solutions of biomacromolecules and discovered the proton signals of mobile water at low temperatures (Kuntz et al 1969;Mathur-De Vre 1979;Siemer et al 2012).…”

Section: Introductionmentioning

confidence: 99%

“…With the aid of hydration studies, the changes in dynamics of macromolecules can be clarified for various environments (Krishman 1996;Wider 1998;Szuminska et al 2001;Foster et al 2007;Rodin 2017;Kerch 2018;Xie et al 2019). Nowadays, NMR gives various tools for successful studying of different molecules and macromolecules of biotechnological systems.…”

Section: Introductionmentioning

confidence: 99%

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NMR techniques in studying water in biotechnological systems

Rodin

2020

Biophys Rev

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Different NMR methodologies have been considered in studying water as a part of the structure of heterogeneous biosystems. The current work mostly describes NMR techniques to investigate slow translational dynamics of molecules affecting anisotropic properties of polymers and biomaterials. With these approaches, information about organized structures and their stability could be obtained in conditions when external factors affect biomolecules. Such changes might include rearrangement of macromolecular conformations at fabrication of nano-scaffolds for tissue engineering applications. The changes in water-fiber interactions could be mirrored by the magnetic resonance methods in various relaxations, double-quantum filtered (DQF), 1D and 2D translational diffusion experiments. These findings effectively demonstrate the current state of NMR studies in applying these experiments to the various systems with the anisotropic properties. For fibrous materials, it is shown how NMR correlation experiments with two gradients (orthogonal or collinear) encode diffusion coefficients in anisotropic materials and how to estimate the permeability of cell walls. It is considered how the DQF NMR technique discovers anisotropic water in natural polymers with various cross-links. The findings clarify hydration sites, dynamic properties, and binding of macromolecules discovering the role of specific states in improving scaffold characteristics in tissue engineering processes. Showing the results in developing these NMR tools, this review focuses on the ways of extracting information about biophysical properties of biomaterials from the NMR data obtained.

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“…Brüschweiler and co-workers 28 , 29 have used differential relaxation times to probe the residue-specific interactions between intrinsically-disordered proteins and silica nanoparticles with negatively-charged surfaces. The binding between intrinsically-disordered proteins and silica nanoparticles has been used to study protein dynamics on timescales that were previously un-reachable 30 .…”

Section: Introductionmentioning

confidence: 99%

Probing driving forces for binding between nanoparticles and amino acids by saturation-transfer difference NMR

Casabianca

2020

Sci Rep

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As nanotechnology becomes increasingly used in biomedicine, it is important to have techniques by which to examine the structure and dynamics of biologically-relevant molecules on the surface of engineered nanoparticles. Previous work has shown that Saturation-Transfer Difference (STD)-NMR can be used to explore the interaction between small molecules, including amino acids, and the surface of polystyrene nanoparticles. Here we use STD-NMR to further explore the different driving forces that are responsible for these interactions. Electrostatic effects are probed by using zwitterionic polystyrene beads and performing STD-NMR experiments at high, low, and neutral pH, as well as by varying the salt concentration and observing the effect on the STD buildup curve. The influence of dispersion interactions on ligand-nanoparticle binding is also explored, by establishing a structureactivity relationship for binding using a series of unnatural amino acids with different lengths of hydrophobic side chains. these results will be useful for predicting which residues in a peptide are responsible for binding and for understanding the driving forces for binding between peptides and nanoparticles in future studies.

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Functional protein dynamics on uncharted time scales detected by nanoparticle-assisted NMR spin relaxation

Cited by 35 publications

References 66 publications

The Ambivalent Role of Proline Residues in an Intrinsically Disordered Protein: From Disorder Promoters to Compaction Facilitators

The Ambivalent Role of Proline Residues in an Intrinsically Disordered Protein: From Disorder Promoters to Compaction Facilitators

NMR techniques in studying water in biotechnological systems

Probing driving forces for binding between nanoparticles and amino acids by saturation-transfer difference NMR

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