Article
Biochemistry & Molecular Biology
Xi Wang, Lavi S. Bigman, Harry M. Greenblatt, Binhan Yu, Yaakov Levy, Junji Iwahara
Summary: This study investigates the mechanism by which D/E repeats in DNA/RNA-binding proteins accelerate the target search process, using experimental and simulation approaches.
NUCLEIC ACIDS RESEARCH
(2023)
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
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)
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)
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)
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
Biochemistry & Molecular Biology
Estella A. Newcombe, Catarina B. Fernandes, Jeppe E. Lundsgaard, Inna Brakti, Kresten Lindorff-Larsen, Annette E. Langkilde, Karen Skriver, Birthe B. Kragelund
Summary: Motifs within proteins help categorize their functions;Intrinsically disordered proteins (IDPs) rich in short linear motifs with various roles;Study found calcium-binding motifs in IDPs may serve various underreported structural and functional roles.
Article
Biochemistry & Molecular Biology
Tamara Ehm, Hila Shinar, Guy Jacoby, Sagi Meir, Gil Koren, Merav Segal Asher, Joanna Korpanty, Matthew P. Thompson, Nathan C. Gianneschi, Michael M. Kozlov, Salome Azoulay-Ginsburg, Roey J. Amir, Joachim O. Raedler, Roy Beck
Summary: Intrinsically disordered peptide amphiphiles (IDPAs) are a novel class of synthetic conjugates that self-assemble into dispersed nanoscopic aggregates or ordered mesophases. Sequence variations in the IDPA systems can significantly alter the headgroup conformation and induce phase transitions, and alterations in the peptide sequence can render IDPAs susceptible to enzymatic cleavage and induce enzymatically activated phase transitions.
Review
Chemistry, Multidisciplinary
Prakash Kulkarni, Supriyo Bhattacharya, Srisairam Achuthan, Amita Behal, Mohit Kumar Jolly, Sourabh Kotnala, Atish Mohanty, Govindan Rangarajan, Ravi Salgia, Vladimir Uversky
Summary: This article discusses the knowledge and unknown areas of intrinsically disordered proteins (IDPs), and explores the influence of IDPs on cell-fate decisions, as well as their potential roles in cellular phenotype switching, biological evolution, proteinaceous organelle formation, and transgenerational inheritance.
Article
Materials Science, Multidisciplinary
Maryam Rahmati, Sabine Stoetzel, Thaqif El Khassawna, Chenyi Mao, Adilijiang Ali, Joshua C. Vaughan, Kamila Iskhahova, D. C. Florian Wieland, Antonio Gonzalez Cantalapiedra, Giuseppe Perale, Felice Betge, Eoghan P. Dillon, Stale Petter Lyngstadaas, Havard Jostein Haugen
Summary: Biomaterial scientists have designed organic bone substitutes based on the biochemical properties of the tissue they mimic, aiming to achieve similar functionality. In this study, two proline-rich disordered peptides (P2 and P6) were incorporated into a biohybrid substitute called SmartBone (R) (SBN). The results showed that these peptides can stimulate bone formation and biomineralization, with P6 being more effective in the early stages while P2 had a stronger effect on later processes. Furthermore, the use of various analysis techniques proved to be valuable in evaluating and diagnosing the structure of bone tissue and the bone-biomaterial interface.
Review
Chemistry, Medicinal
Junxi Mu, Hao Liu, Jian Zhang, Ray Luo, Hai-Feng Chen
Summary: Intrinsically disordered proteins (IDPs) play crucial roles in biological processes and are associated with various diseases. Molecular dynamics simulation is a valuable tool for quantifying IDP structures, but faces limitations. Recent force field strategies aim to improve accuracy, but further advancements are needed.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Multidisciplinary Sciences
Rajkama, Nisal, P. Jitendra, Agata, Susan, Geoff, W. Aaron, J. Anita, Namita Roy, K. Naba
Summary: This study reveals the impact of crowding on the dynamic conformation of intrinsically disordered proteins (IDPs). Through experimental methods and model construction, researchers found that crowding can induce specific conformational changes in IDPs. This study is of great importance for a better understanding of the interactions and structural dynamics of IDPs in crowded environments.
Article
Chemistry, Physical
Florencia Klein, Exequiel E. Barrera, Sergio Pantano
Summary: The CG SIRAH force field shows a good ability to describe the dynamical behavior of IDPs and unstructured peptides, and it can effectively capture the effect of point mutations in loosely structured peptides.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2021)
Article
Biochemistry & Molecular Biology
Surl-Hee Ahn, Gary A. Huber, J. Andrew McCammon
Summary: Intrinsically disordered proteins (IDPs) have attracted significant attention due to their involvement in biological processes and diseases. Computational studies using Brownian dynamics (BD) simulations with a coarse-grained force field for proteins (COFFDROP) have been conducted to complement experimental work. The researchers found that IDPs' properties, such as hydrodynamic radii and entanglement indices, are influenced by salt concentration.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Karen E. Lee, Rebecca Procopio, Jose S. Pulido, Kammi B. Gunton
Summary: Intrinsically disordered regions (IDRs) are protein regions that lack stable tertiary structures and play important roles in signaling and regulation through dynamic interactions. Understanding IDRs and their association with biological function may shed light on the development of inherited retinal diseases (IRDs). This study aims to investigate the level of disorder in 14 proteins related to IRDs and its correlation with the number of pathogenic missense variants.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Anne Bremer, Mina Farag, Wade M. Borcherds, Ivan Peran, Erik W. Martin, Rohit Pappu, Tanja Mittag
Summary: This study uncovers how evolutionarily conserved compositional biases influence the phase behavior of Prion-like low-complexity domains (PLCDs). Tyrosine is identified as a stronger sticker, while lysine weakens sticker-sticker interactions. Additionally, glycine and serine residues act as non-equivalent spacers, impacting the driving forces for phase separation in PLCDs.
Article
Multidisciplinary Sciences
Ian Seim, Ammon E. Posey, Wilton T. Snead, Benjamin M. Stormo, Daphne Klotsa, Rohit Pappu, Amy S. Gladfelter
Summary: This study reveals a mechanism that influences the composition of ribonucleoprotein bodies, in which specific sequence motifs and synergies with the intrinsically disordered region drive the formation of oligomers in the dilute phase, hindering its incorporation into the dense phase. This finding provides new insights for designing synthetic ribonucleoprotein bodies.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Xiangze Zeng, Kiersten M. Ruff, Rohit Pappu
Summary: Polyampholytes are the most common type of intrinsically disordered proteins (IDPs), characterized by low net charge and high fractions of charged residues. Recent experiments have revealed differences in conformational preferences for different sequences of polyampholytic IDPs, as well as the existence of various conformations including globules and self-avoiding walks. Atomistic simulations have shown that these IDPs generally sample two stable states, with globules favored by electrostatic attractions and self-avoiding walks favored by favorable hydration energies. The temperature at which these states coexist depends on the sequence, with arginine-rich sequences preferring globular conformations and lysine-rich sequences preferring self-avoiding walks. The length of the side chain also affects the conformational preferences, with shorter side chains favoring necklace-like conformations. Overall, these findings provide insights into the relationship between sequence and conformation in polyampholytic IDPs.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Cell Biology
Douglas R. Kellogg, Petra Anne Levin
Summary: Pioneering work discovered that bacterial cell size is proportional to growth rate set by nutrient availability, known as the growth law. Recent studies have shown that the relationship between growth rate, nutrients, and cell size is more complex than originally thought.
TRENDS IN CELL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Marina Feric, Azadeh Sarfallah, Furqan Dar, Dmitry Temiakov, Rohit Pappu, Tom Misteli
Summary: In live cells, phase separation can organize macromolecules into membraneless structures called biomolecular condensates. Through in vitro experiments, it has been found that mitochondrial components can form multiphasic, viscoelastic condensates, and the transcriptional rates mediated by condensates are lower than in solution, which is associated with the formation of vesicle-like structures driven by the production and accumulation of RNA during transcription.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Chemistry, Physical
Martin J. Fossat, Ammon E. Posey, Rohit V. Pappu
Summary: The single alpha helix (SAH) is a recurring motif in biology. The sequence with consensus E4K4 repeats shows insensitivity to pH, and the preference for uncharged glutamate residues in internal positions of SAH-forming sequences contributes to this insensitivity. The stability of alpha helical conformations increases with the number of E4K4 repeats, allowing for a larger range of charge states that are compatible with high helical content.
Article
Biophysics
Mina Farag, Alex S. Holehouse, Xiangze Zeng, Rohit V. Pappu
Summary: Biomolecular condensates form through phase transitions of biomacromolecules specific to the condensates. Intrinsically disordered regions with appropriate sequence grammars can contribute to the driving forces for phase separation of multivalent proteins through homotypic and heterotypic interactions. Experiments and computations have advanced to the point where the concentrations of coexisting dense and dilute phases can be measured or computed for individual intrinsically disordered regions. The development of computational tools like FIREBALL enables efficient analysis and fitting of experimental or computed data of binodals, providing insight into the coil-to-globule transitions of macromolecules.
BIOPHYSICAL JOURNAL
(2023)
Review
Chemistry, Multidisciplinary
Rohit Pappu, Samuel R. Cohen, Furqan Dar, Mina Farag, Mrityunjoy Kar
Summary: In this review, we discuss the role of multivalent associative biomacromolecules, such as proteins and nucleic acids, in the formation and regulation of biomolecular condensates. We also explore the concepts of phase transitions in aqueous solutions of these associative biomacromolecules and their relevance to biomolecular condensates.
Article
Biochemistry & Molecular Biology
Xiangze Zeng, Rohit V. Pappu
Summary: Biomolecular condensates are specific cellular structures that can organize cellular matter and biochemical reactions in space and time. They are formed and dissolved through spontaneous and driven phase transitions of multivalent associative macromolecules. Current progress has focused on modeling sequence-specific phase transitions, especially for intrinsically disordered proteins. In this review, we summarize the state-of-the-art theories and computations aimed at understanding and modeling sequence-specific, thermodynamically controlled, coupled associative and segregative phase transitions of archetypal multivalent macromolecules.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2023)
Article
Chemistry, Physical
Jared M. Lalmansingh, Alex T. Keeley, Kiersten M. Ruff, Rohit V. Pappu, Alex S. Holehouse
Summary: Conformational heterogeneity is a characteristic feature of intrinsically disordered proteins and protein regions. Simulations based on atomistic and coarse-grained models are commonly used to understand the sequence-specific interactions and functions of these proteins. In this study, a new analysis toolkit called SOURSOP is introduced, which provides a collection of easy-to-use functions to characterize the conformational ensembles of intrinsically disordered proteins.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2023)
Article
Chemistry, Multidisciplinary
Gable M. Wadsworth, Walter J. Zahurancik, Xiangze Zeng, Paul Pullara, Lien B. Lai, Vaishnavi Sidharthan, Rohit V. Pappu, Venkat Gopalan, Priya R. Banerjee
Summary: Co-phase separation of RNAs and RNA-binding proteins is an important driving force for the biogenesis of ribonucleoprotein granules. It has been discovered that RNA can also undergo phase transitions in the absence of proteins, driven by entropy and modulated by RNA bases. The presence of magnesium ions enables RNA-only condensates to also undergo percolation transitions, leading to arrested condensates.
Article
Multidisciplinary Sciences
Mina Farag, Wade M. Borcherds, Anne Bremer, Tanja Mittag, Rohit V. Pappu
Summary: Through simulations and experiments, researchers found that mixtures of RNA-binding proteins' PLCDs undergo phase separation more readily than individual PLCDs due to complementary electrostatic interactions. They revealed how stoichiometric ratios of different components and their sequence-encoded interactions contribute to the driving forces for condensate formation, and how interaction strengths and sequence lengths modulate conformational preferences of molecules at condensates' interfaces.
NATURE COMMUNICATIONS
(2023)