A Sharp Thermal Transition of Fast Aromatic‐Ring Dynamics in Ubiquitin

Kasinath, Vignesh; Fu, Yinan; Sharp, Kim A.; Wand, A. Joshua

doi:10.1002/ange.201408220

Cited by 14 publications

(23 citation statements)

References 32 publications

(44 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, new cases have been reported (Weininger et al 2014b;Yang et al 2015) enabled by methodological advances in site-selective 13 C labeling (Lundström et al 2007;Teilum et al 2006), aromatic 13 C relaxation dispersion experiments (Weininger et al 2012(Weininger et al , 2014a and the understanding of strong 1 H-1 H couplings (Weininger et al 2013). Additionally, ring flips can be studied by long scale MD simulations (Shaw et al 2010) and extremely fast ring flips are shown to affect order parameters (Kasinath et al 2015). So far, ring flips in all but one system (Nall and Zuniga 1990) are of aromatic residues without specific interactions, like aromatic-aromatic pair interactions Petsko 1985, 1989) and interactions with cations (Mahadevi and Sastry 2013) or sulfur (Valley et al 2012).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Slow ring flips in aromatic cluster of GB1 studied by aromatic 13C relaxation dispersion methods

2020

View full text Add to dashboard Cite

Ring flips of phenylalanine and tyrosine are a hallmark of protein dynamics. They report on transient breathing motions of proteins. In addition, flip rates also depend on stabilizing interactions in the ground state, like aromatic stacking or cation-π interaction. So far, experimental studies of ring flips have almost exclusively been performed on aromatic rings without stabilizing interactions. Here we investigate ring flip dynamics of Phe and Tyr in the aromatic cluster in GB1. We found that all four residues of the cluster, Y3, F30, Y45 and F52, display slow ring flips. Interestingly, F52, the central residue of the cluster, which makes aromatic contacts with all three others, is flipping significantly faster, while the other rings are flipping with the same rates within margin of error. Determined activation enthalpies and activation volumes of these processes are in the same range of other reported ring flips of single aromatic rings. There is no correlation of the number of aromatic stacking interactions to the activation enthalpy, and no correlation of the ring's extent of burying to the activation volume. Because of these findings, we speculate that F52 is undergoing concerted ring flips with each of the other rings.

show abstract

Section: Introductionmentioning

confidence: 99%

“…A connection with the energy of a ring flip is not known. For extremely fast ring flips, that affect order parameters, no sizeable pressure effect was observed (Kasinath et al 2015).…”

Section: Introductionmentioning

confidence: 99%

Slow ring flips in aromatic cluster of GB1 studied by aromatic 13C relaxation dispersion methods

2020

View full text Add to dashboard Cite

show abstract

“…Phenylalanine residues have been implicated as important markers of dynamical transitions, 7, 31 as motions of bulky aromatic groups often require accommodations of the entire core. 32–35 We have recently observed a solvent-driven dynamical transition for a phenylalanine residue in the core of globular villin headpiece subdomain (HP36) that did not entirely disappear in the dry protein, but rather showed a transition temperature which was 80° higher.…”

Section: Introductionmentioning

confidence: 99%

Solvent-Driven Dynamical Crossover in the Phenylalanine Side-Chain from the Hydrophobic Core of Amyloid Fibrils Detected by ²H NMR Relaxation

et al. 2017

View full text Add to dashboard Cite

Aromatic residues are important markers of dynamical changes in proteins’ hydrophobic cores. In this work we investigated the dynamics of the F19 side-chain in the core of amyloid fibrils across a wide temperature range of 300 to 140 K. We utilized solid-state 2H NMR relaxation to demonstrate the presence of a solvent-driven dynamical cross-over between different motional regimes, often also referred to as the dynamical transition. In particular, the dynamics are dominated by small-angle fluctuations at low temperatures and by π-flips of the aromatic ring at high temperatures. The cross-over temperature is more than 43 degrees lower for the hydrated state of the fibrils compared to the dry state, indicating that interactions with water facilitate π-flips. Further, cross-over temperatures are shown to be very sensitive to polymorphic states of the fibrils, such as the 2-fold and 3-fold symmetric morphologies of the wild-type protein as well as D23N mutant protofibrils. We speculate that these differences can be attributed, at least partially, to enhanced interactions with water in the 3-fold polymorph, which has been shown to have a water-accessible cavity. Combined with previous studies of methyl group dynamics, the results highlight the presence of multiple dynamics modes in the core of the fibrils, which was originally believed to be quite rigid.

show abstract

“…The dynamics of these groups are known to be sensitive not only to local fluctuations but also to the overall hydrophobic core environment. 3–12 The assessment of the dynamics of aromatic side chains in a protein is relatively technically challenging, and much fewer studies are dedicated to these sites 13–23 compared with the investigations of protein methyl groups. Aromatic side chains comprise about 25% of the core volume on average and are often solvent-protected in the core by flanking methyl groups.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2015

View full text Add to dashboard Cite

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.

show abstract

A Sharp Thermal Transition of Fast Aromatic‐Ring Dynamics in Ubiquitin

Cited by 14 publications

References 32 publications

Slow ring flips in aromatic cluster of GB1 studied by aromatic 13C relaxation dispersion methods

Slow ring flips in aromatic cluster of GB1 studied by aromatic 13C relaxation dispersion methods

Solvent-Driven Dynamical Crossover in the Phenylalanine Side-Chain from the Hydrophobic Core of Amyloid Fibrils Detected by ²H NMR Relaxation

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

Contact Info

Product

Resources

About

A Sharp Thermal Transition of Fast Aromatic‐Ring Dynamics in Ubiquitin

Cited by 14 publications

References 32 publications

Slow ring flips in aromatic cluster of GB1 studied by aromatic 13C relaxation dispersion methods

Slow ring flips in aromatic cluster of GB1 studied by aromatic 13C relaxation dispersion methods

Solvent-Driven Dynamical Crossover in the Phenylalanine Side-Chain from the Hydrophobic Core of Amyloid Fibrils Detected by 2H NMR Relaxation

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

Contact Info

Product

Resources

About

Solvent-Driven Dynamical Crossover in the Phenylalanine Side-Chain from the Hydrophobic Core of Amyloid Fibrils Detected by ²H NMR Relaxation