scholarly journals Temperature-dependent structural changes in intrinsically disordered proteins: Formation of α-helices or loss of polyproline II?

2010 ◽  
Vol 19 (8) ◽  
pp. 1555-1564 ◽  
Author(s):  
Magnus Kjaergaard ◽  
Ann-Beth Nørholm ◽  
Ruth Hendus-Altenburger ◽  
Stine F. Pedersen ◽  
Flemming M. Poulsen ◽  
...  
Keyword(s):  
Structural Changes ◽  
Intrinsically Disordered Proteins ◽  
Disordered Proteins ◽  
Temperature Dependent ◽  
Intrinsically Disordered ◽  
Polyproline Ii

From folding to function: complex macromolecular reactions unraveled one-by-one with optical tweezers

2021 ◽  
Author(s):  
Pétur O. Heidarsson ◽  
Ciro Cecconi
Keyword(s):  
Optical Tweezers ◽  
Single Molecule ◽  
Structural Changes ◽  
Intrinsically Disordered Proteins ◽  
Conformational Dynamics ◽  
Disordered Proteins ◽  
Kinase Activation ◽  
Intrinsically Disordered ◽  
Complex Protein ◽  
Methodological Principles

Abstract Single-molecule manipulation with optical tweezers has uncovered macromolecular behaviour hidden to other experimental techniques. Recent instrumental improvements have made it possible to expand the range of systems accessible to optical tweezers. Beyond focusing on the folding and structural changes of isolated single molecules, optical tweezers studies have evolved into unraveling the basic principles of complex molecular processes such as co-translational folding on the ribosome, kinase activation dynamics, ligand–receptor binding, chaperone-assisted protein folding, and even dynamics of intrinsically disordered proteins (IDPs). In this mini-review, we illustrate the methodological principles of optical tweezers before highlighting recent advances in studying complex protein conformational dynamics – from protein synthesis to physiological function – as well as emerging future issues that are beginning to be addressed with novel approaches.

scholarly journals Genetically tunable frustration controls allostery in an intrinsically disordered transcription factor

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Jing Li ◽  
Jordan T White ◽  
Harry Saavedra ◽  
James O Wrabl ◽  
Hesam N Motlagh ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
Structural Changes ◽  
Intrinsically Disordered Proteins ◽  
Tertiary Structure ◽  
Control Function ◽  
Disordered Proteins ◽  
Intrinsically Disordered ◽  
Novel Strategy ◽  
Structured Proteins

Intrinsically disordered proteins (IDPs) present a functional paradox because they lack stable tertiary structure, but nonetheless play a central role in signaling, utilizing a process known as allostery. Historically, allostery in structured proteins has been interpreted in terms of propagated structural changes that are induced by effector binding. Thus, it is not clear how IDPs, lacking such well-defined structures, can allosterically affect function. Here, we show a mechanism by which an IDP can allosterically control function by simultaneously tuning transcriptional activation and repression, using a novel strategy that relies on the principle of ‘energetic frustration’. We demonstrate that human glucocorticoid receptor tunes this signaling in vivo by producing translational isoforms differing only in the length of the disordered region, which modulates the degree of frustration. We expect this frustration-based model of allostery will prove to be generally important in explaining signaling in other IDPs.

scholarly journals Hydrodynamic Radii of Intrinsically Disordered Proteins Determined from Experimental Polyproline II Propensities

2016 ◽  
Vol 12 (1) ◽  
pp. e1004686 ◽  
Author(s):  
Maria E. Tomasso ◽  
Micheal J. Tarver ◽  
Deepa Devarajan ◽  
Steven T. Whitten
Keyword(s):  
Intrinsically Disordered Proteins ◽  
Disordered Proteins ◽  
Intrinsically Disordered ◽  
Polyproline Ii

scholarly journals Design of intrinsically disordered proteins that undergo phase transitions with lower critical solution temperatures

2020 ◽  
Author(s):  
Xiangze Zeng ◽  
Chengwen Liu ◽  
Martin J. Fossat ◽  
Pengyu Ren ◽  
Ashutosh Chilkoti ◽  
...  
Keyword(s):  
Phase Separation ◽  
Phase Behavior ◽  
Intrinsically Disordered Proteins ◽  
Disordered Proteins ◽  
Temperature Dependent ◽  
Intrinsically Disordered ◽  
Implicit Solvation Model ◽  
Theta Temperature ◽  
Behavior Systems ◽  
Critical Solution Temperatures

AbstractMany naturally occurring elastomers are intrinsically disordered proteins (IDPs) built up of repeating units and they can demonstrate two types of thermoresponsive phase behavior. Systems characterized by lower critical solution temperatures (LCST) undergo phase separation above the LCST whereas systems characterized by upper critical solution temperatures (UCST) undergo phase separation below the UCST. There is congruence between thermoresponsive coil-globule transitions and phase behavior whereby the theta temperatures above or below which the IDPs transition from coils to globules serve as useful proxies for the LCST / UCST values. This implies that one can design sequences with desired values for the theta temperature with either increasing or decreasing radii of gyration above the theta temperature. Here, we show that the Monte Carlo simulations performed in the so-called intrinsic solvation (IS) limit version of the temperature-dependent ABSINTH implicit solvation model, yields a useful heuristic for discriminating between sequences with known LCST versus UCST phase behavior. Accordingly, we use this heuristic in a supervised approach, integrate it with a genetic algorithm, combine this with IS limit simulations, and demonstrate that novel sequences can be designed with LCST phase behavior. These calculations are aided by direct estimates of temperature dependent free energies of solvation for model compounds that are derived using the polarizable AMOEBA forcefield. To demonstrate the validity of our designs, we calculate coil-globule transition profiles using the full ABSINTH model and combine these with Gaussian Cluster Theory calculations to establish the LCST phase behavior of designed IDPs.

scholarly journals Glycine Rich Segments Adopt Polyproline II Helices Which May Contribute to Biomolecular Condensate Formation

2020 ◽  
Author(s):  
Miguel Mompean ◽  
Bethan S. McAvan ◽  
Sara S. Felix ◽  
Miguel Trevino ◽  
Javier Oroz ◽  
...  
Keyword(s):  
Intrinsically Disordered Proteins ◽  
Cd Spectroscopy ◽  
Disordered Proteins ◽  
Nmr Studies ◽  
Intrinsically Disordered ◽  
The Third ◽  
Fused In Sarcoma ◽  
Polyproline Ii ◽  
Polyproline Ii Helix ◽  
Dynamics Simulations

Many intrinsically disordered proteins contain Gly-rich regions which are generally assumed to be disordered. Such regions often form biomolecular condensates which play essential roles in organizing cellular processes. However, the bases of their formation and stability are still not completely understood. Considering NMR studies of the Gly-rich H. harveyi "snow flea" antifreeze protein, we recently proposed that Gly-rich sequences, such as the third "RGG" region of Fused in Sarcoma (FUS) protein, may adopt polyproline II helices whose association might stabilize condensates. Here, this hypothesis is tested with a polypeptide corresponding to the third RGG region of FUS. NMR spectroscopy and molecular dynamics simulations suggest that significant populations of polyproline II helix are present. These findings are corroborated in a model peptide Ac-RGGYGGRGGWGGRGGY-NH2, where a peak characteristic of polyproline II helix is observed using CD spectroscopy. Its intensity suggests a polyproline II population of 40%. This result is supported by data from FTIR and NMR spectroscopies. In the latter, NOE correlations are observed between the Tyr and Arg, and Arg and Trp side chain hydrogens, confirming that side chains spaced three residues apart are close in space. Taken together, the data are consistent with a polyproline II helix, which is bent to optimize interactions between guanidinium and aromatic moieties, in equilibrium with a statistical coil ensemble. In cells, the polyproline II population of these peptides could be augmented by binding profilin protein or SH3, WW or OCRE domains, association with RNA or assembly into polyproline II helical bundles. These results lend credence to the hypothesis that Gly-rich segments of disordered proteins may form polyproline II helices which help stabilize biomolecular condensates.

scholarly journals Affinity of IDPs to their targets is modulated by ion-specific changes in kinetics and residual structure

2017 ◽  
Vol 114 (37) ◽  
pp. 9882-9887 ◽  
Author(s):  
Basile I. M. Wicky ◽  
Sarah L. Shammas ◽  
Jane Clarke
Keyword(s):  
Structural Changes ◽  
Intrinsically Disordered Proteins ◽  
Disordered Proteins ◽  
Marginal Stability ◽  
Residual Structure ◽  
Intrinsically Disordered ◽  
Folded Proteins ◽  
The Stability ◽  
Ion Profiles

Intrinsically disordered proteins (IDPs) are characterized by a lack of defined structure. Instead, they populate ensembles of rapidly interconverting conformations with marginal structural stabilities. Changes in solution conditions such as temperature and crowding agents consequently affect IDPs more than their folded counterparts. Here we reveal that the residual structure content of IDPs is modulated both by ionic strength and by the type of ions present in solution. We show that these ion-specific structural changes result in binding affinity shifts of up to sixfold, which happen through alteration of both association and dissociation rates. These effects follow the Hofmeister series, but unlike the well-established effects on the stability of folded proteins, they already occur at low, hypotonic concentrations of salt. We attribute this sensitivity to the marginal stability of IDPs, which could have physiological implications given the role of IDPs in signaling, the asymmetric ion profiles of different cellular compartments, and the role of ions in biology.

Monitoring structural changes in intrinsically disordered proteins using QCM-D: application to the bacterial cell division protein ZipA

2016 ◽  
Vol 52 (39) ◽  
pp. 6541-6544 ◽  
Author(s):  
Pablo Mateos-Gil ◽  
Achilleas Tsortos ◽  
Marisela Vélez ◽  
Electra Gizeli
Keyword(s):  
Cell Division ◽  
Structural Changes ◽  
Intrinsically Disordered Proteins ◽  
Intrinsically Disordered Protein ◽  
Disordered Proteins ◽  
Bacterial Cell Division ◽  
Intrinsically Disordered ◽  
Disordered Protein ◽  
Cell Division Protein

Characterization of structural changes in an intrinsically disordered protein attached on a QCM-D, with a sensitivity of 1.8 nm or better.

scholarly journals Protein Plasticity and its Role in Cellular Functions

2020 ◽  
Author(s):  
Sidra Ilyas ◽  
Abdul Manan
Keyword(s):  
Conformational Changes ◽  
Structural Changes ◽  
Intrinsically Disordered Proteins ◽  
Redox Homeostasis ◽  
Redox Status ◽  
Disordered Proteins ◽  
Redox Activity ◽  
Cellular Functions ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions

ABSTRACTThe contribution of redox active properties of cysteines in intrinsically disordered regions (IDRs) of proteins is not very well acknowledged. Despite of providing structural stability and rigidity, intrinsically disordered cysteines are exceptional redox sensors and the redox status of the protein defines its structure. Experimental evidence suggests that the conformational heterogeneity of cysteines in intrinsically disordered proteins (IDPs) is related to numerous functions including regulation, structural changes and fuzzy complex formation. The unusual plasticity of IDPs make them suitable candidate to interact with many clients under specific conditions. Binding capabilities, dimerization and folding or unfolding nature of IDPs upon interaction with multiple clients assign distinct conformational changes associated with disulfide formation. Here we are going to focus on redox activity of IDPs, their dramatic roles that are not only restricted to cellular redox homeostasis and signaling pathways but also provide antioxidant, anti-apoptotic, binding and interactive power.

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