Noncovalent Dimerization of Ubiquitin

Liu, Zhu; Zhang, Wei Ping; Xing, Qiong; Ren, Xuefeng; Liu, Maili; Tang, Chun

doi:10.1002/anie.201106190

Cited by 81 publications

(124 citation statements)

References 38 publications

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“…In this study, we set the dielectric constant and focus on physiological salt concentrations of (lead to the Debye screening length 10 ) which are consistent with the experimental condition [22]. All charged residues were assigned charges according to their electrostatic properties at neutral pH 7.…”

Section: Methodsmentioning

confidence: 99%

PolyUbiquitin Chain Linkage Topology Selects the Functions from the Underlying Binding Landscape

et al. 2014

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Ubiquitin (Ub) can generate versatile molecular signals and lead to different celluar fates. The functional poly-valence of Ub is believed to be resulted from its ability to form distinct polymerized chains with eight linkage types. To provide a full picture of ubiquitin code, we explore the binding landscape of two free Ub monomers and also the functional landscapes of of all eight linkage types by theoretical modeling. Remarkably, we found that most of the compact structures of covalently connected dimeric Ub chains (diUbs) pre-exist on the binding landscape. These compact functional states were subsequently validated by corresponding linkage models. This leads to the proposal that the folding architecture of Ub monomer has encoded all functional states into its binding landscape, which is further selected by different topologies of polymeric Ub chains. Moreover, our results revealed that covalent linkage leads to symmetry breaking of interfacial interactions. We further propose that topological constraint not only limits the conformational space for effective switching between functional states, but also selects the local interactions for realizing the corresponding biological function. Therefore, the topological constraint provides a way for breaking the binding symmetry and reaching the functional specificity. The simulation results also provide several predictions that qualitatively and quantitatively consistent with experiments. Importantly, the K48 linkage model successfully predicted intermediate states. The resulting multi-state energy landscape was further employed to reconcile the seemingly contradictory experimental data on the conformational equilibrium of K48-diUb. Our results further suggest that hydrophobic interactions are dominant in the functional landscapes of K6-, K11-, K33- and K48 diUbs, while electrostatic interactions play a more important role in the functional landscapes of K27, K29, K63 and linear linkages.

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Section: Methodsmentioning

confidence: 99%

PolyUbiquitin Chain Linkage Topology Selects the Functions from the Underlying Binding Landscape

et al. 2014

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“…If a sufficiently large database of interactions were available, it might even be conceivable to use statistical methods to parametrize the patchiness of proteinprotein interactions without first extensively simulating the system. From an experimental viewpoint, careful studies of weak protein-protein interactions, as has recently been done for ubiquitin in solution would also be of much help [148]. Studying the structure of transient complexes in solution [149] may not only help identify potential crystal contacts, but also competing interactions that can hinder crystal assembly.…”

Section: Conclusion and Open Questionsmentioning

confidence: 99%

Soft matter perspective on protein crystal assembly

Fusco

Charbonneau

2016

Colloids and Surfaces B: Biointerfaces

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“…31 While the N-state conformation is made up of α-helix and β-sheet structural elements, partially unfolded structures are elongated, typically take on more charge, and possess substantially more α-helical character. 32 Ubiquitin also contains 12 basic residues, many of which are located near the surface of the folded structure, 33 meaning that when these residues are protonated they should readily solvate by large numbers of water molecules. Therefore, our expectation was that ESI−cryo-IM-MS would reveal the preservation of hydrated ubiquitin ions of low charge states (6 + to 8 + ), occupying the folded N-state conformation.…”

Section: ■ Protein Hydration Behaviormentioning

confidence: 99%

“…Previous NMR studies have also shown that noncovalent dimers of ubiquitin can form upon the creation of a hydrophobic binding interface between the β-sheet regions of both ions, specifically between hydrophobic patches within the interface referred to as "hot spots". 33 This implies that both the hydrophobic effect and the presence of ionic H-bonds play essential roles in driving the dimerization of ubiquitin ions in solution. Exclusion of water from this buried hydrophobic region may promote hydration of the surrounding charged residues and further mediate the binding event through formation of stabilizing "water bridges" between hydrophilic sites.…”

Section: ■ Protein Hydration Behaviormentioning

confidence: 99%

Cryogenic Ion Mobility-Mass Spectrometry: Tracking Ion Structure from Solution to the Gas Phase

et al. 2016

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Electrospray ionization (ESI) combined with ion mobility-mass spectrometry (IM-MS) is adding new dimensions, that is, structure and dynamics, to the field of biological mass spectrometry. There is increasing evidence that gas-phase ions produced by ESI can closely resemble their solution-phase structures, but correlating these structures can be complicated owing to the number of competing effects contributing to structural preferences, including both inter- and intramolecular interactions. Ions encounter unique hydration environments during the transition from solution to the gas phase that will likely affect their structure(s), but many of these structural changes will go undetected because ESI-IM-MS analysis is typically performed on solvent-free ions. Cryogenic ion mobility-mass spectrometry (cryo-IM-MS) takes advantage of the freeze-drying capabilities of ESI and a cryogenically cooled IM drift cell (80 K) to preserve extensively solvated ions of the type [M + xH](x+)(H2O)n, where n can vary from zero to several hundred. This affords an experimental approach for tracking the structural evolution of hydrated biomolecules en route to forming solvent-free gas-phase ions. The studies highlighted in this Account illustrate the varying extent to which dehydration can alter ion structure and the overall impact of cryo-IM-MS on structural studies of hydrated biomolecules. Studies of small ions, including protonated water clusters and alkyl diammonium cations, reveal structural transitions associated with the development of the H-bond network of water molecules surrounding the charge carrier(s). For peptide ions, results show that water networks are highly dependent on the charge-carrying species within the cluster. Specifically, hydrated peptide ions containing lysine display specific hydration behavior around the ammonium ion, that is, magic number clusters with enhanced stability, whereas peptides containing arginine do not display specific hydration around the guanidinium ion. Studies on the neuropeptide substance P illustrate the ability of cryo-IM-MS to elucidate information about heterogeneous ion populations. Results show that a kinetically trapped conformer is stabilized by a combination of hydration and specific intramolecular interactions, but upon dehydration, this conformer rearranges to form a thermodynamically favored gas-phase ion conformation. Finally, recent studies on hydration of the protein ubiquitin reveal water-mediated dimerization, thereby illustrating the extension of this approach to studies of large biomolecules. Collectively, these studies illustrate a new dimension to studies of biomolecules, resulting from the ability to monitor snapshots of the structural evolution of ions during the transition from solution to gas phase and provide unparalleled insights into the intricate interplay between competing effects that dictate conformational preferences.

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Noncovalent Dimerization of Ubiquitin

Cited by 81 publications

References 38 publications

PolyUbiquitin Chain Linkage Topology Selects the Functions from the Underlying Binding Landscape

PolyUbiquitin Chain Linkage Topology Selects the Functions from the Underlying Binding Landscape

Soft matter perspective on protein crystal assembly

Cryogenic Ion Mobility-Mass Spectrometry: Tracking Ion Structure from Solution to the Gas Phase

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