Article
Biochemistry & Molecular Biology
Pinak Chakrabarti, Devlina Chakravarty
Summary: Proteins can have different structures, ranging from rigid to flexible to completely disordered. Intrinsic disorder proteins (IDPs) or specific intrinsically disordered regions (IDRs) can form complexes that would be otherwise impossible, providing the flexibility needed for specific functions. IDRs can bind multiple partners and act as hubs in protein-protein interaction networks. The disorder-to-order transition during binding provides specificity and reversibility. The interactions of IDRs can be modulated by the environment or covalent modifications, and their mis-signalling or non-native folding may lead to diseases.
BIOPHYSICAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Rebecca B. Berlow, H. Jane Dyson, Peter E. Wright
Summary: Intrinsically disordered proteins compete for binding to common regulatory targets to carry out their biological functions. The activation domains of HIF-1 alpha and CITED2 function as a unidirectional, allosteric molecular switch to control transcription of adaptive genes. The mechanistic details of this molecular switch were characterized through NMR spectroscopy and biophysical methods, revealing the contributions of individual binding motifs in CITED2. These findings provide insight into the complexity of molecular interactions involving disordered proteins and how they compete for occupancy of common targets.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
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)
Article
Biochemistry & Molecular Biology
Vincent D. Maciej, Nevena Mateva, Juliane Schwarz, Theresa Dittmers, Megha Mallick, Henning Urlaub, Sutapa Chakrabarti
Summary: The study reveals a weak interaction between the RNA-binding protein TTP and the decapping enzyme DCP2, which affects the stability of transcripts containing AU-rich elements (AREs). The interaction involves disordered regions of both proteins and leads to the assembly of phase-separated droplets. These findings highlight the significance of weak interactions in cellular functionality.
NUCLEIC ACIDS RESEARCH
(2022)
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
Chemistry, Physical
Antonio B. Oliveira, Xingcheng Lin, Prakash Kulkarni, Jose N. Onuchic, Susmita Roy, Vitor B. P. Leite
Summary: The newly developed energy landscape visualization method ELViM is applied to explore the frustrated energy landscapes of the intrinsically disordered protein PAGE4. Analysis of atomistic trajectories and energy landscapes using ELViM reveals how phosphorylation affects the conformational diversity and functional mechanisms of different phosphoforms of PAGE4, shedding light on their interactions with proteins such as c-Jun.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2021)
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.
Review
Chemistry, Multidisciplinary
Matti Mar, Kateryna Nitsenko, Petur O. Heidarsson
Summary: Eukaryotic transcription factors play a crucial role in integrating molecular feedback and regulating gene expression. They consist of structured DNA-binding domains and long intrinsically disordered regions (IDRs). The dynamic multifunctionality of IDRs is essential for their functions in genome regulation. This review analyzes the chemical features of TF IDRs and their involvement in protein interactions, DNA binding, chromatin opening, and phase separation. Suggestions are given for future research to integrate experiments and simulations in understanding TF functions.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
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.
Article
Biochemistry & Molecular Biology
Jorge Marcos-Viquez, Annia Rodriguez-Hernandez, Laura I. Alvarez-Anorve, Andrea Medina-Garcia, Jacqueline Plumbridge, Mario L. Calcagno, Adela Rodriguez-Romero, Ismael Bustos-Jaimes
Summary: This study describes the regulatory mechanism of Glucosamine-6-phosphate deaminase SdNagBII from Shewanella denitrificans using enzyme kinetics, isothermal titration calorimetry (ITC), and X-ray crystallography. The experiments revealed two different binding sites with distinctive thermodynamic signatures for the allosteric activator GlcNAc6P and the transition-state analog GlcNol6P. Crystallographic data demonstrated the presence of an unusual allosteric site that can bind both GlcNAc6P and GlcNol6P, suggesting that the homotropic activation of this enzyme arises from the occupation of the allosteric site by the substrate. This study unveils a novel mechanism to generate a high degree of homotropic activation in SdNagBII.
Article
Biochemistry & Molecular Biology
Ilinka Clerc, Amin Sagar, Alessandro Barducci, Nathalie Sibille, Pau Bernado, Juan Cortes
Summary: Intrinsically disordered proteins and regions play crucial roles in biological processes by performing specialized functions related to the recognition of other biomolecules. Computational approaches have become essential tools for understanding the functional mechanisms of these proteins due to their conformational heterogeneity.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
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.