Review
Biochemistry & Molecular Biology
Rachel Evans, Sravani Ramisetty, Prakash Kulkarni, Keith Weninger
Summary: Intense study of intrinsically disordered proteins (IDPs) began in the late 1990s and revealed their important functions. Over the past two decades, it has become clear that IDPs play critical roles in various biological phenomena. The application of integrative structural biology has emerged as an essential approach to understanding IDP phenomena.
Article
Biology
Utsab R. Shrestha, Jeremy C. Smith, Loukas Petridis
Summary: The study demonstrates that enhancing the sampling using Hamiltonian replica exchange molecular simulation (HREMD) leads to accurate unbiased ensembles of intrinsically disordered proteins. Standard molecular simulation cannot reproduce small-angle scattering data as well as HREMD, highlighting the utility of the suggested approach.
COMMUNICATIONS BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Gil Koren, Sagi Meir, Lennard Holschuh, Haydyn D. T. Mertens, Tamara Ehm, Nadav Yahalom, Adina Golombek, Tal Schwartz, Dmitri I. Svergun, Omar A. Saleh, Joachim Dzubiella, Roy Beck
Summary: Short-range interactions and long-range contacts drive the folding of proteins. The structure of proteins directly affects their biological function. Nearly 40% of eukaryotes proteome is composed of intrinsically disordered proteins (IDPs) and protein regions that fluctuate between ensembles of numerous conformations. Polymer physics can, to some level, relate the IDP's sequence to its ensemble conformations, but long-range contacts between distant amino acids play a crucial role in determining intramolecular structures.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Aditya Mittal, Anandkumar Madhavjibhai Changani, Sakshi Taparia
Summary: This study identified unique signatures of intrinsic disorder by systematically synthesizing different peptide libraries, expanding the known intrinsically disordered proteins and providing a major advancement in exploring the functional manifestations of such proteins.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Review
Biochemistry & Molecular Biology
Rakesh Trivedi, Hampapathalu Adimurthy Nagarajaram
Summary: This review discusses different aspects of disordered proteins and protein regions, as well as the experimental and computational methods used to characterize them. Additionally, the role of disordered proteins in diseases and their potential as drug targets are explored.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Steffen Luedeke, Philipp Lohner, Lara G. Stuehn, Martin U. Betschart, Matthias C. Huber, Andreas Schreiber, Stefan M. Schiller
Summary: Research has shown that coacervation of Elastin-like proteins occurs sharply when a certain number of repeat units has acquired beta-turn conformation, which is retained even after polypeptide assembly. This conformational threshold may have implications for other protein assembly processes and the design of protein-based smart materials.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Nanoscience & Nanotechnology
Noriyuki Kodera, Daisuke Noshiro, Sujit K. Dora, Tetsuya Mori, Johnny Habchi, David Blocquel, Antoine Gruet, Marion Dosnon, Edoardo Salladini, Christophe Bignon, Yuko Fujioka, Takashi Oda, Nobuo N. Noda, Mamoru Sato, Marina Lotti, Mineyuki Mizuguchi, Sonia Longhi, Toshio Ando
Summary: High-speed atomic force microscopy imaging can provide a semiquantitative, realistic description of the dynamic structure of intrinsically disordered proteins, which dynamically sample a multitude of conformational states, making their structural analysis difficult.
NATURE NANOTECHNOLOGY
(2021)
Article
Chemistry, Physical
Z. Mitrinova, M. Chenkova, N. Denkov, S. Tcholakova
Summary: The effect of different types of surfactants with varying chain lengths on the surface properties of a mixed solution of SLES and CAPB was studied. It was found that the addition of longer cosurfactant chains decreases the surface tension of the solution. Nonionic surfactants showed a particularly deep minimum in dynamic surface tension. The addition of anionic surfactants did not affect the dynamic and equilibrium surface tensions of the solution. A strong correlation was established between the dynamic surface tension and the viscosity of the concentrated solution for nonionic surfactants.
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
(2022)
Article
Chemistry, Multidisciplinary
Guy Jacoby, Merav Segal Asher, Tamara Ehm, Inbal Abutbul Ionita, Hila Shinar, Salome Azoulay-Ginsburg, Ido Zemach, Gil Koren, Dganit Danino, Michael M. Kozlov, Roey J. Amir, Roy Beck
Summary: This study introduces a new type of peptide amphiphiles, intrinsically disordered peptide amphiphiles (IDPA), that exhibit a sharp pH-induced micellar phase-transition. The shape transition can serve as a mechanism for the design of cargo hold-and-release applications, demonstrating the potential of tailoring interactions between disordered peptides for various stimuli-responsive biomedical applications.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Biochemistry & Molecular Biology
Ellen Rieloff, Marie Skepo
Summary: Phosphorylation plays a crucial role in regulating the function of intrinsically disordered proteins, with the distribution of phosphorylated and positively charged residues throughout the sequence impacting the formation of salt bridges. Understanding the structural implications of phosphorylation remains a challenge, as factors beyond net charge, such as specific residue interactions, can influence the global dimensions of disordered proteins.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Kiersten M. Ruff, Rohit Pappu
Summary: Accurate predictions of protein structures using AlphaFold have made significant progress. Most protein sequences in the human proteome have been structurally annotated, with over 30% of regions being disordered.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Chemistry, Medicinal
Eric Fagerberg, Marie Skepo
Summary: Coarse-graining is commonly used to reduce computational cost in simulations, but it is known to have lower transferability and accuracy for systems beyond its parametrization scope. In this study, we compared the performance of a bead-necklace model and a modified Martini 2 model, both coarse-grained models, using a set of intrinsically disordered proteins with different degrees of coarse-graining. The results showed that the naive expectation of the least coarse-grained model performing the best was not true, indicating that a more advanced model is not necessarily better in model choice.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Chemistry, Physical
Mauro Lorenzo Mugnai, D. Thirumalai
Summary: The study presents a theoretical method to investigate the impact of pH changes on the conformational ensemble of intrinsically disordered proteins. By generalizing the molecular transfer model and utilizing a mean-field approximation, the research explores the effects of charged groups' precise locations on the structural properties of model IDPs under varying protonation states. The study demonstrates that this computational tool can effectively study the properties of IDPs and other biological systems as a function of pH.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2021)
Review
Biochemistry & Molecular Biology
H. Jane Dyson
Summary: Viruses infect all kingdoms of life and employ disordered proteins to accomplish various functions. Disordered proteins have been discovered in almost all viruses studied, regardless of the viral genome composition or the viral capsid configuration. This review presents a collection of stories illustrating the diverse functions of disordered proteins in viruses, providing a survey of the field's expansion.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Myriam Guillien, Assia Mouhand, Aurelie Fournet, Amandine Gontier, Aleix Marti Navia, Tiago N. Cordeiro, Frederic Allemand, Aurelien Thureau, Jean-Louis Baneres, Pau Bernado, Nathalie Sibille
Summary: This study used an integrated biophysical strategy to describe the basal conformations of the C-terminal domains of three class A GPCRs, and revealed the presence of transient secondary structures in these regions that may be involved in interaction with arrestin. The findings provide insights into the molecular mechanisms of GPCR signal transduction.
Correction
Chemistry, Multidisciplinary
Yuri Gerelli, Amanda Eriksson Skog, Stephanie Jephthah, Rebecca J. L. Welbourn, Alexey Klechikov, Marie Skepo
Article
Biochemistry & Molecular Biology
Samuel Lenton, Stefan Hervo-Hansen, Anton M. Popov, Mark D. Tully, Mikael Lund, Marie Skepo
Summary: Re-entrant condensation occurs when a condensed protein regime forms between two critical ion concentrations. Attractive interactions between arginine and tripolyphosphate are found to determine the condensation and decondensation boundaries of cationic proteins. These findings provide insights into the organizational mechanism that can be used to tune protein interactions in solution.
Article
Biochemistry & Molecular Biology
Ellen Rieloff, Marie Skepo
Summary: Phosphorylation is a common post-translational modification in intrinsically disordered proteins, and computer simulations are useful tools to study its effects. In this study, CHARMM36m consistently produced more compact conformations with a higher content of bends in phosphorylated peptides compared to Amber ff99SB-ILDN+TIP4P-D. Despite a reduction in salt-bridging probability, changes in ionic strength had negligible effects on the conformational ensembles.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Physical
Stephanie Jephthah, Francesco Pesce, Kresten Lindorff-Larsen, Marie Skepo
Summary: This study compared the performance of four different force fields in simulating the PPII structure of five peptides, revealing that all force fields are able to capture PPII structures but with varying degrees of affinity to other secondary structure elements. Cluster analysis of simulations showed significant differences in the conformational ensembles of the force fields, indicating a need for further experiments and methods to assess the accuracy of force fields in determining PPII structure.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2021)
Article
Biochemistry & Molecular Biology
Ellen Rieloff, Marie Skepo
Summary: Phosphorylation plays a crucial role in regulating the function of intrinsically disordered proteins, with the distribution of phosphorylated and positively charged residues throughout the sequence impacting the formation of salt bridges. Understanding the structural implications of phosphorylation remains a challenge, as factors beyond net charge, such as specific residue interactions, can influence the global dimensions of disordered proteins.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Physical
Eric Fagerberg, Samuel Lenton, Tommy Nylander, Tilo Seydel, Marie Skepo
Summary: This study investigates the dynamical properties of Histatin 5, an intrinsically disordered protein, under self-crowding conditions. Quasi-elastic neutron scattering and molecular dynamics simulations are used to analyze the diffusion behavior. The results show that diffusion decreases significantly under crowding, possibly due to aggregation at higher protein concentrations. The temperature effects largely follow Stokes-Einstein behavior. Simple geometric considerations fail to predict diffusion rates accurately, while simulations show some agreement with experiments. The scaling law previously used for globular proteins is found inadequate for Histatin 5, highlighting the distinct characteristics of intrinsically disordered proteins.
JOURNAL OF PHYSICAL CHEMISTRY B
(2022)
Article
Biochemistry & Molecular Biology
Mona Koder Hamid, Linda K. Mansson, Viktoriia Meklesh, Per Persson, Marie Skepo
Summary: This study investigates the structural changes of an intrinsically disordered protein (IDP) when it adsorbs to a solid surface. Molecular dynamics simulations and experimental results were used to compare and analyze the changes. The study found that adsorption increases the helical content and polyproline II helices of the protein, and extends its conformation. Simulations B, E, and G showed better agreement with experimental results than other simulations.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Correction
Chemistry, Multidisciplinary
Yuri Gerelli, Amanda Eriksson Skog, Stephanie Jephthah, Rebecca J. L. Welbourn, Alexey Klechikov, Marie Skepoe
Article
Chemistry, Medicinal
Eric Fagerberg, Marie Skepo
Summary: Coarse-graining is commonly used to reduce computational cost in simulations, but it is known to have lower transferability and accuracy for systems beyond its parametrization scope. In this study, we compared the performance of a bead-necklace model and a modified Martini 2 model, both coarse-grained models, using a set of intrinsically disordered proteins with different degrees of coarse-graining. The results showed that the naive expectation of the least coarse-grained model performing the best was not true, indicating that a more advanced model is not necessarily better in model choice.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Chemistry, Multidisciplinary
Amanda E. Skog, Giacomo Corucci, Mark D. Tully, Giovanna Fragneto, Yuri Gerelli, Marie Skepo
Summary: Histatin 5 is a protein in saliva that acts as a defense against oral candidiasis. It forms a protein cushion under a model bilayer due to electrostatic interactions. Changing the number of histidines in the peptide sequence affects the penetration depth of the peptide into the bilayer.
Article
Chemistry, Physical
Simon Fridolf, Mona Koder Hamid, Leo Svenningsson, Marie Skepo, Emma Sparr, Daniel Topgaard
Summary: In this study, the impact of ganglioside GM3 on the bilayer structure and dynamics of C-H bond segments was investigated using solid-state NMR spectroscopy and molecular dynamics simulations. The findings revealed that GM3 affects the dynamical properties of POPC membranes, providing important insights into interactions with other biomolecules.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2022)
Article
Nanoscience & Nanotechnology
Sara Haddadi, Marie Skepo, Jan Forsman
Summary: In this study, polystyrene particles carrying short polyethylene glycol (PEG) chains were synthesized and the temperature-dependent aggregation and dispersion behavior was experimentally verified. Interestingly, repulsive polymer-mediated interactions were found at intermediate temperatures, while attractive interactions were observed at room temperature and high temperatures, leading to either flocculation or phase separation of particles. Fine-tuned theoretical models based on experimental results displayed semi-quantitative accuracy in predicting temperature-dependent stability of the system.
ACS NANOSCIENCE AU
(2021)
Article
Chemistry, Multidisciplinary
Jacopo Cautela, Bjoern Stenqvist, Karin Schillen, Domagoj Belic, Linda K. Mansson, Fabian Hagemans, Maximilian Seuss, Andreas Fery, Jerome J. Crassous, Luciano Galantini
Article
Chemistry, Physical
Linda K. Mansson, Feifei Peng, Jerome J. Crassous, Peter Schurtenberger