Defining Noncovalent Ubiquitin Homodimer Interfacial Interactions through Comparisons with Covalently Linked Diubiquitin

Wagner, Nicole D.; Russell, David H.

doi:10.1021/jacs.6b09829

Cited by 17 publications

(34 citation statements)

References 28 publications

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“…Overall, our analysis revealed the involvement of many charged residues in the Ub-Ub interface and suggests that K63-Ub2 prefer electrostatic interfacial contacts, being hindered by steric constraints to interact via the common I44/I36 hydrophobic patches, in line with previous reports 65 .…”

Section: Validation and Analysis Of The Ub-ub Interfacessupporting

confidence: 91%

Determination of Protein Structural Ensembles by Hybrid-Resolution SAXS Restrained Molecular Dynamics.

Paissoni¹,

Jussupow²,

Camilloni

2019

Preprint

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<div><div><div><p>SAXS experiments provide low-resolution but valuable information about the dynamics of biomolecular systems, which could be ideally integrated into MD simulations to accurately determine conformational ensembles of flexible proteins. The applicability of this strategy is hampered by the high computational cost required to calculate scattering intensities from three-dimensional structures. We previously presented a hybrid resolution method that makes atomistic SAXS-restrained MD simulation feasible by adopting a coarse-grained approach to efficiently back-calculate scattering intensities; here, we extend this technique, applying it in the framework of metainference with the aim to investigate the dynamical behavior of flexible biomolecules. The efficacy of the method is assessed on the K63-diubiquitin, showing that the inclusion of SAXS-restraints is effective in generating a reliable conformational ensemble, improving the agreement with independent experimental data.</p></div></div></div>

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Section: Validation and Analysis Of The Ub-ub Interfacessupporting

confidence: 91%

Determination of Protein Structural Ensembles by Hybrid-Resolution SAXS Restrained Molecular Dynamics.

Paissoni¹,

Jussupow²,

Camilloni

2019

Preprint

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“…Further evidence supporting the proposed mechanism for water‐mediated formation of the Ubq dimer comes from studies on the CIU of the noncovalent dimer and the K‐6, K‐11, K‐48, and K‐63 covalent dimers. The K‐48 dimer is known to contain strong interactions involving the I‐44 hydrophobic patch, and the CIU heat maps for the K‐48 and noncovalent dimer are almost identical (Wagner & Russell, 2016).…”

Section: Water‐mediated Dimerization Of Ubqmentioning

confidence: 99%

“…Similarities between the unfolding pathways of noncovalent and K48‐linked ubiquitin dimers ( B and E , respectively) suggest the noncovalent dimer adopts similar subunit interfacial interactions to the K48‐linked covalent ubiquitin dimer. CIU heatmaps are reproduced from references Wagner and Russell (2016); Wagner et al (2017). CIU, collision‐induced unfolding; NMR, nuclear magnetic resonance.…”

Section: Stabilities Of Gas‐phase Protein Ions: Ciumentioning

confidence: 99%

The Ims Paradox: A Perspective on Structural Ion Mobility‐mass Spectrometry

McCabe

Hebert

Shirzadeh

et al. 2020

Mass Spectrometry Reviews

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Studies of large proteins, protein complexes, and membrane protein complexes pose new challenges, most notably the need for increased ion mobility (IM) and mass spectrometry (MS) resolution. This review covers evolutionary developments in IM‐MS in the authors' and key collaborators' laboratories with specific focus on developments that enhance the utility of IM‐MS for structural analysis. IM‐MS measurements are performed on gas phase ions, thus “structural IM‐MS” appears paradoxical—do gas phase ions retain their solution phase structure? There is growing evidence to support the notion that solution phase structure(s) can be retained by the gas phase ions. It should not go unnoticed that we use “structures” in this statement because an important feature of IM‐MS is the ability to deal with conformationally heterogeneous systems, thus providing a direct measure of conformational entropy. The extension of this work to large proteins and protein complexes has motivated our development of Fourier‐transform IM‐MS instruments, a strategy first described by Hill and coworkers in 1985 (Anal Chem, 1985, 57, pp. 402–406) that has proved to be a game‐changer in our quest to merge drift tube (DT) and ion mobility and the high mass resolution orbitrap MS instruments. DT‐IMS is the only method that allows first‐principles determinations of rotationally averaged collision cross sections (CSS), which is essential for studies of biomolecules where the conformational diversities of the molecule precludes the use of CCS calibration approaches. The Fourier transform‐IM‐orbitrap instrument described here also incorporates the full suite of native MS/IM‐MS capabilities that are currently employed in the most advanced native MS/IM‐MS instruments. © 2020 John Wiley & Sons Ltd. Mass Spec Rev

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“…The noncovalent association of Ub monomers was recently detected using paramagnetic relaxation enhancement (PRE) NMR studies, which suggested that the dimer structure of Ub resembled K48 linked Ub 2 . Another report using collision‐induced unfolding ion mobility‐mass spectrometry showed that the noncovalent Ub 2 exhibited similar interfacial interactions and structural stability as K48 linked Ub 2 . However, recently reported crystal structure of Ub monomers showed an arrangement of four subunits in the asymmetric crystal unit resembling the structure of K11 linked Ub 2 .…”

Section: Introductionmentioning

confidence: 99%

Residual Dipolar‐Coupling‐Based Conformational Comparison of Noncovalent Ubiquitin Homodimer with Covalently Linked Diubiquitin

et al. 2020

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Although the conformation of the polymer chain of Ubiquitin (Ub) mainly depends on the type of isopeptide linkage connecting two Ub molecules, the non-covalent (noncovalent) interaction between two Ub molecules within the chain could also tune their conformational preference. Here, we studied the conformation of noncovalently formed Ub dimers in solution using residual dipolar couplings (RDCs). Comparing the RDC derived alignment tensor of the noncovalently formed dimer with the two most abundant (K11 and K48) covalent linked Ub dimers revealed that the conformation of K11 linked and noncovalent Ub dimers were similar. Between the various NMR and crystal structures of K11 linked Ub dimers, RDC tensor analysis showed that the structure of K11 linked dimer crystalized at neutral pH is similar to noncovalent dimer. Analogous to the experimental study, the comparison of predicted order matrix of various covalent Ub dimers with that of the experimentally determined order matrix of noncovalent Ub dimer also suggests that the conformation of K11 linked dimers crystalized at neutral pH is similar to the noncovalent dimer.

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Defining Noncovalent Ubiquitin Homodimer Interfacial Interactions through Comparisons with Covalently Linked Diubiquitin

Cited by 17 publications

References 28 publications

Determination of Protein Structural Ensembles by Hybrid-Resolution SAXS Restrained Molecular Dynamics.

Determination of Protein Structural Ensembles by Hybrid-Resolution SAXS Restrained Molecular Dynamics.

The Ims Paradox: A Perspective on Structural Ion Mobility‐mass Spectrometry

Residual Dipolar‐Coupling‐Based Conformational Comparison of Noncovalent Ubiquitin Homodimer with Covalently Linked Diubiquitin

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