Decoding the Mobility and Time Scales of Protein Loops

Gu, Yina; Li, Da Wei; Brüschweiler, Rafael

doi:10.1021/ct501085y

Cited by 39 publications

(42 citation statements)

References 46 publications

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“…Although we cannot verify our hypothesis in this case, we believe that this channel could be activated by warm stimuli as in the case of TRPV4 . The mobile nature of protein loops has also been decoded in terms of composition, being Lys, Met, and Asp, part of “fast” loops (as in TRPM8 S4‐S5L), while Cys, Tyr, Ile Phe, and Leu are often part of static loops (as in TRPV1, and V2), which is consistent with our results. Nevertheless, although internal motion (flexibility) importantly depends on aminoacid composition, several other factors have to be considered to make a universal postulate about this.…”

Section: Discussionsupporting

confidence: 86%

Side chain flexibility and coupling between the S4‐S5 linker and the TRP domain in thermo‐sensitive TRP channels: Insights from protein modeling

2017

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Section: Discussionsupporting

confidence: 86%

Side chain flexibility and coupling between the S4‐S5 linker and the TRP domain in thermo‐sensitive TRP channels: Insights from protein modeling

2017

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“…48. C. Proposed mass-altered bond vibrational modes in the 1 H, While the length, amino acid composition, and the presence of hydrogen-bonds can all affect loop motions, 68 loops often interact with each other in order to gate their motions. 69,70 An illustrative example can be found in E. coli DHFR.…”

Section: Modulation Of Loop Dynamicsmentioning

confidence: 99%

Engineered control of enzyme structural dynamics and function

2018

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Enzymes undergo a range of internal motions from local, active site fluctuations to large-scale, global conformational changes. These motions are often important for enzyme function, including in ligand binding and dissociation and even preparing the active site for chemical catalysis. Protein engineering efforts have been directed towards manipulating enzyme structural dynamics and conformational changes, including targeting specific amino acid interactions and creation of chimeric enzymes with new regulatory functions. Post-translational covalent modification can provide an additional level of enzyme control. These studies have not only provided insights into the functional role of protein motions, but they offer opportunities to create stimulus-responsive enzymes. These enzymes can be engineered to respond to a number of external stimuli, including light, pH, and the presence of novel allosteric modulators. Altogether, the ability to engineer and control enzyme structural dynamics can provide new tools for biotechnology and medicine.

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“…The growth of Protein Data Bank (PDB) redundancy, refinement and development of techniques such as NMR, SAXS and single molecule spectroscopy over the last years have allowed the experimental characterization of a large number of protein ensembles 2,3 . Structural differences between conformers could result from the relative movements of large domains as rigid bodies 4 , secondary and tertiary element rearrangements 5 , and loop movements 6 . Apparently, most globular proteins have very few conformers describing their native state to achieve their functions.…”

Section: Introductionmentioning

confidence: 99%

Ensembles from ordered and disordered proteins reveal similar structural constraints during evolution

Marchetti

Monzón

Tosatto

et al. 2018

Preprint

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Inter-residue contacts determine the structural properties for each conformer in the ensembles describing the native state of proteins. Structural constraints during evolution could then provide biologically relevant information about the conformational ensembles and their relationship with protein function. Here, we studied the proportion of sites evolving under structural constraints in two very different types of ensembles, those coming from ordered or disordered proteins. Using a structurally constrained model of protein evolution we found that both types of ensembles show comparable, near 40%, number of positions evolving under structural constraints. Among these sites, ~68% are in disordered regions and ~57% of them show long-range inter-residue contacts. Also, we found that disordered ensembles are redundant in reference to their structurally constrained evolutionary information and could be described on average with ~11 conformers. Despite the different complexity of the studied ensembles and proteins, the similar constraints reveal a comparable level of selective pressure to maintain their biological functions.These results highlight the importance of the evolutionary information to recover meaningful biological information to further characterize conformational ensembles.

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Decoding the Mobility and Time Scales of Protein Loops

Cited by 39 publications

References 46 publications

Side chain flexibility and coupling between the S4‐S5 linker and the TRP domain in thermo‐sensitive TRP channels: Insights from protein modeling

Side chain flexibility and coupling between the S4‐S5 linker and the TRP domain in thermo‐sensitive TRP channels: Insights from protein modeling

Engineered control of enzyme structural dynamics and function

Ensembles from ordered and disordered proteins reveal similar structural constraints during evolution

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