Protein Surface and Core Dynamics Show Concerted Hydration‐Dependent Activation

Wood, Kathleen; Gallat, François-Xavier; Otten, Renee; Heel, Auke J. van; Lethier, Mathilde; Eijck, Lambert van; Moulin, Martine; Haertlein, Michael; Weik, Martin H.; Mulder, Frans A. A.

doi:10.1002/ange.201205898

Cited by 10 publications

(11 citation statements)

References 42 publications

(24 reference statements)

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“…Our earlier studies on HP36 protein indicated that introduction of this level of hydration has the effect of dramatically enhancing the dynamics on µs‐ms time scale of both surface‐exposed and hydrophobic core residues in comparison with the dry state. This results is consistent with several studies, in particular with a recent work by Wood et al ., as well as with the work by Tamura et al . The latter work also demonstrated that the dynamics in hydrated powder state is very similar to what was observed in crystalline state.…”

Section: Resultssupporting

confidence: 93%

Effect of subdomain interactions on methyl group dynamics in the hydrophobic core of villin headpiece protein

Vugmeyster

Ostrovsky

et al. 2013

Protein Science

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Thermostable villin headpiece protein (HP67) consists of the N-terminal subdomain (residues 10-41) and the autonomously folding C-terminal subdomain (residues 42-76) which pack against each other to form a structure with a unified hydrophobic core. The X-ray structures of the isolated C-terminal subdomain (HP36) and its counterpart in HP67 are very similar for the hydrophobic core residues. However, fine rearrangements of the free energy landscape are expected to occur because of the interactions between the two subdomains. We detect and characterize these changes by comparing the ms-ms time scale dynamics of the methyl-bearing side chains in isolated HP36 and in HP67. Specifically, we probe three hydrophobic side chains at the interface of the two subdomains (L42, V50, and L75) as well as at two residues far from the interface (L61 and L69). Solid-state deuteron NMR techniques are combined with computational modeling for the detailed characterization of motional modes in terms of their kinetic and thermodynamic parameters. The effect of interdomain interactions on side chain dynamics is seen for all residues but L75. Thus, changes in dynamics because of subdomain interactions are not confined to the site of perturbation. One of the main results is a two-to threefold increase in the value of the activation energies for the rotameric mode of motions in HP67 compared with HP36. Detailed analysis of configurational entropies and heat capacities complement the kinetic view of the degree of the disorder in the folded state.

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Section: Resultssupporting

confidence: 93%

Effect of subdomain interactions on methyl group dynamics in the hydrophobic core of villin headpiece protein

Vugmeyster

Ostrovsky

et al. 2013

Protein Science

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“…The main sample conditions are hydrated powders with a water content of 40%, which is a typical amount of water for protein powder samples. 47–50 We confirmed the refolding procedure by measuring the 15 N backbone chemical shifts of the three core phenylalanines and additional leucine residues 45, 51 (Supporting Information SI1). An additional dry sample labeled at the F58 residue corresponds to lyophilized powder without the reintroduction of water.…”

Section: Methodsmentioning

confidence: 54%

Dynamics of Hydrophobic Core Phenylalanine Residues Probed by Solid-State Deuteron NMR

et al. 2015

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We conducted a detailed investigation of the dynamics of two phenylalanine side chains in the hydrophobic core of the villin headpiece subdomain protein (HP36) in the hydrated powder state over the 298–80 K temperature range. Our main tools were static deuteron NMR measurements of longitudinal relaxation and line shapes supplemented with computational modeling. The temperature dependence of the relaxation times reveals the presence of two main mechanisms that can be attributed to the ring-flips, dominating at high temperatures, and small-angle fluctuations, dominating at low temperatures. The relaxation is non-exponential at all temperatures with the extent of non-exponentiality increasing from higher to lower temperatures. This behavior suggests a distribution of conformers with unique values of activation energies. The central values of the activation energies for the ring-flipping motions are among the smallest reported for aromatic residues in peptides and proteins and point to a very mobile hydrophobic core. The analysis of the widths of the distributions, in combination with the earlier results on the dynamics of flanking methyl groups (Vugmeyster et al., J. Phys. Chem. B 2013, 117, 6129–6137), suggests that the hydrophobic core undergoes slow concerted fluctuations. There is a pronounced effect of dehydration on the ring-flipping motions, which shifts the distribution toward more rigid conformers. The cross-over temperature between the regions of dominance of the small-angle fluctuations and ring-flips shifts from 195 K in the hydrated protein to 278 K in the dry one. This result points to the role of solvent in softening the core and highlights aromatic residues as markers of the protein dynamical transitions.

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“…(43, 44) Hydration level dependence can be important for assessing the effect of the solvent on the onset of motions. (45–48) Hydration levels up to about 60–80% by weight can be investigated without introducing the effects of overall tumbling (i.e., dissolving protein) for globular proteins. For samples such as such as amyloid fibrils comprising the amyloid-β protein, water levels can be higher due to negligible effect of tumbling for the large fibril aggregates.…”

Section: Experimental Approachesmentioning

confidence: 99%

Static solid-state 2H NMR methods in studies of protein side-chain dynamics

Vugmeyster

Ostrovsky

2017

Progress in Nuclear Magnetic Resonance Spectroscopy

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In this review, we discuss the experimental static deuteron NMR techniques and computational approaches most useful for the investigation of side-chain dynamics in protein systems. Focus is placed on the interpretation of line shape and relaxation data within the framework of motional modeling. We consider both jump and diffusion models and apply them to uncover glassy behaviors, conformational exchange and dynamical transitions in proteins. Applications are chosen from globular and membrane proteins, amyloid fibrils, peptide adsorbed on surfaces and proteins specific to connective tissues.

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Protein Surface and Core Dynamics Show Concerted Hydration‐Dependent Activation

Cited by 10 publications

References 42 publications

Effect of subdomain interactions on methyl group dynamics in the hydrophobic core of villin headpiece protein

Effect of subdomain interactions on methyl group dynamics in the hydrophobic core of villin headpiece protein

Dynamics of Hydrophobic Core Phenylalanine Residues Probed by Solid-State Deuteron NMR

Static solid-state 2H NMR methods in studies of protein side-chain dynamics

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