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
Cell Biology
Yannick R. R. Brunet, Cameron Habib, Anna P. P. Brogan, Lior Artzi, David Z. Z. Rudner
Summary: In this study, the roles of intrinsically disordered protein regions (IDRs) in bacteria were investigated, and it was reported that extracytoplasmic IDRs in Bacillus subtilis are required for cell wall homeostasis. The data support a model in which the IDR on anti-sigma factor RsgI senses gaps in the PG meshwork and activates sigma(I), while the IDR on PBP1 directs the synthase to these sites to fortify them.
GENES & DEVELOPMENT
(2022)
Article
Biochemistry & Molecular Biology
Jaime Santos, Irantzu Pallares, Valentin Iglesias, Salvador Ventura
Summary: The prevalence of cryptic amyloidogenic regions (CARs) of polar nature in intrinsically disordered regions (IDRs) has been explored. CARs are associated with protein function and interactions, but also carry a risk of malfunction. The existence of ancestral CARs may have evolved into functional interacting regions, playing a significant role in protein evolution at the origins of life.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
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
Biochemistry & Molecular Biology
Mariane Goncalves-Kulik, Pablo Mier, Kristina Kastano, Juan Cortes, Pau Bernado, Friederike Schmid, Miguel A. Andrade-Navarro
Summary: This study provides evidence that low complexity regions (LCRs) within intrinsically disordered regions (IDRs) of proteins can induce local structure. By predicting IDRs in the human proteome and analyzing structures in the Protein Data Bank (PDB), the researchers found that LCRs were more likely to have structural information assigned to them compared to surrounding IDRs. The most frequent LCRs containing E (Glu) or G (Gly) were found to induce helical or coil structures. These findings suggest a structuring role of LCRs within IDRs.
Review
Biochemistry & Molecular Biology
Denisa Jamecna, Bruno Antonny
Summary: Membrane contact sites are regions of close apposition between membrane-bound organelles, where proteins, including lipid transfer proteins, display various domain organization. Intrinsic disordered protein regions play multiple roles in LTPs, such as serving as flexible tethers between membranes, entropic barriers, and defining the action range of catalytic domains. These functions, along with mediating protein-protein and protein-membrane interactions, require fine coordination for the efficiency and fidelity of contact sites.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2021)
Review
Biochemistry & Molecular Biology
Amit Chaudhary, Pankaj Kumar Chaurasia, Sandeep Kushwaha, Pallavi Chauhan, Aakash Chawade, Ashutosh Mani
Summary: Cold shock proteins are a conserved family of proteins that play important roles in low-temperature stress response and nucleic acid binding in bacteria. They are involved in various cellular and metabolic processes in prokaryotes and have been found to be crucial in the progression of cancer and Alzheimer's disease in humans.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Biology
Taraneh Zarin, Bob Strome, Gang Peng, Iva Pritisanac, Julie D. Forman-Kay, Alan M. Moses
Summary: This study aims to utilize molecular features within the intrinsically disordered regions (IDRs) of proteins to predict specific biological functions and identify associated features. The results show diverse predictable functions, with some features consistent with previous reports and others previously unknown. Feature analysis represents a new systematic approach to understanding how biological functions of IDRs are determined by their protein sequences.
Review
Biochemistry & Molecular Biology
David Moses, Garrett M. Ginell, Alex S. Holehouse, Shahar Sukenik
Summary: Intrinsically disordered proteins and protein regions (IDRs) play essential roles in eukaryotic organisms. Unlike folded proteins, IDRs exist in a conformational ensemble influenced by sequence-dependent interactions. The absence of a stable 3D structure and high solvent accessibility make IDRs inherently sensitive to environmental changes, allowing them to act as sensors and actuators of cellular physicochemistry.
TRENDS IN BIOCHEMICAL SCIENCES
(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
Biochemistry & Molecular Biology
Carlos Pintado-Grima, Oriol Barcenas, Zoe Manglano-Artunedo, Rita Vilaca, Sandra Macedo-Ribeiro, Irantzu Pallares, Jaime Santos, Salvador Ventura
Summary: Proteome-wide analyses have revealed that amyloidogenic regions are present in most globular proteins, while being underrepresented in intrinsically disordered proteins (IDPs). However, recent research has shown that intrinsically disordered regions (IDRs) do contain significant amyloid load in the form of cryptic amyloidogenic regions (CARs), which are exposed to solvent and are more polar than conventional amyloid regions. CARs are associated with both IDPs function and malfunction, and their presence is linked to pathologies such as cancer and Alzheimer's disease. To explore these previously unnoticed amyloidogenic regions, CARs-DB, a database containing precomputed predictions for all CARs in the IDPs deposited in the DisProt database, was developed. CARs-DB allows for easy access to a large number of unique CARs and has been validated by demonstrating the amyloidogenic potential of selected CARs.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Cell Biology
Melody Subra, Manuela Dezi, Joelle Bigay, Sandra Lacas-Gervais, Aurelie Di Cicco, Ana Rita Dias Araujo, Sophie Abelanet, Lucile Fleuriot, Delphine Debayle, Romain Gautier, Amanda Patel, Fanny Roussi, Bruno Antonny, Daniel Levy, Bruno Mesmin
Summary: Membrane contact sites (MCSs) are diverse in shape, composition, and dynamics. VAP proteins play a crucial role in the formation of MCSs involving the endoplasmic reticulum (ER). The localization and function of VAP-A in different MCSs depend on its intrinsically disordered regions (IDRs). IDRs do not affect VAP-A's preference for specific partners but adjust its geometry to MCS organization and lifetime constraints, ensuring membrane tethering plasticity and efficiency.
DEVELOPMENTAL CELL
(2023)
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)
Article
Chemistry, Medicinal
Katarzyna Walczewska-Szewc, Wieslaw Nowak
Summary: Traditional techniques fail to capture the structural reorganizations of protein disordered regions, making it difficult to assess their functions solely based on experiments. To address this, we used computational molecular dynamics simulations to study the dynamics of disordered regions in the Kir6.2/SUR1 potassium channel. Our findings shed light on the action of this critical complex.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Biology
Raghavendar R. Sanganna Gari, Grigory Tagiltsev, Ruth A. Pumroy, Yining Jiang, Martin Blackledge, Vera Y. Moiseenkova-Bell, Simon Scheuring
Summary: This study used high-speed atomic force microscopy to image TRPV2 channels in membranes and found that the N-terminal intrinsically disordered regions (IDRs) were involved in intermolecular interactions. The results provide evidence about the 'structure' of TRPV2 IDRs and suggest their potential role in mediating protein-protein interactions.
COMMUNICATIONS BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Toni I. Gossmann, Achchuthan Shanmugasundram, Stefan Boerno, Ludovic Duvaux, Christophe Lemaire, Heiner Kuhl, Sven Klages, Lee D. Roberts, Sophia Schade, Johanna M. Gostner, Falk Hildebrand, Jakob Vowinckel, Coraline Bichet, Michael Muelleder, Enrica Calvani, Aleksej Zelezniak, Julian L. Griffin, Peer Bork, Dominique Allaine, Aurelie Cohas, John J. Welch, Bernd Timmermann, Markus Ralser
Article
Plant Sciences
Mathias Bockwoldt, Ines Heiland, Karsten Fischer
Review
Biochemistry & Molecular Biology
Fabrizio Clarelli, Jingyi Liang, Antal Martinecz, Ines Heiland, Pia Abel zur Wiesch
CELLULAR AND MOLECULAR LIFE SCIENCES
(2020)
Article
Multidisciplinary Sciences
Cormac M. Kinsella, Francisco J. Ruiz-Ruano, Anne-Marie Dion-Cote, Alexander J. Charles, Toni I. Gossmann, Josefa Cabrero, Dennis Kappei, Nicola Hemmings, Mirre J. P. Simons, Juan Pedro M. Camacho, Wolfgang Forstmeier, Alexander Suh
NATURE COMMUNICATIONS
(2019)
Review
Biochemistry & Molecular Biology
Anze Zupanic, Hans C. Bernstein, Ines Heiland
CELLULAR AND MOLECULAR LIFE SCIENCES
(2020)
Editorial Material
Genetics & Heredity
Toni I. Gossmann, Markus Ralser
TRENDS IN GENETICS
(2020)
Article
Biochemistry & Molecular Biology
Leeban Yusuf, Matthew C. Heatley, Joseph P. G. Palmer, Henry J. Barton, Christopher R. Cooney, Toni Gossmann
Article
Multidisciplinary Sciences
Oyvind Stromland, Juha P. Kallio, Annica Pschibul, Renate H. Skoge, Hulda M. Hardardottir, Lars J. Sverkeli, Thorsten Heinekamp, Olaf Kniemeyer, Marie Migaud, Mikhail Makarov, Toni Gossmann, Axel A. Brakhage, Mathias Ziegler
Summary: Nicotinamide adenine dinucleotide (NAD) plays a crucial role in cellular bioenergetics and signalling. Fungal NADases on the surface of Aspergillus fumigatus and Neurospora crassa exhibit unique biochemical and structural properties, suggesting potential advantages during interactions with hosts or competing microorganisms.
NATURE COMMUNICATIONS
(2021)
Correction
Multidisciplinary Sciences
Oyvind Stromland, Juha P. Kallio, Annica Pschibul, Renate H. Skoge, Hulda M. Hardardottir, Lars J. Sverkeli, Thorsten Heinekamp, Olaf Kniemeyer, Marie Migaud, Mikhail V. Makarov, Toni I. Gossmann, Axel A. Brakhage, Mathias Ziegler
Summary: A correction has been published for this paper, and the link is provided for reference.
NATURE COMMUNICATIONS
(2021)
Article
Microbiology
Falk Hildebrand, Toni Gossmann, Clemence Frioux, Ezgi Ozkurt, Pernille Neve Myers, Pamela Ferretti, Michael Kuhn, Mohammad Bahram, Henrik Bjorn Nielsen, Peer Bork
Summary: Human gut bacterial strains can persist for decades in individuals, families, and geographic regions, with locally successful strains of Bacteroidota showing high levels of genetic adaptation. By contrast, Firmicutes rely on weak phylogeographic patterns but strong family transmissions, likely related to sporulation. These analyses provide insights into long-term persistence of gut microbes and the implications for gut flora modulations.
CELL HOST & MICROBE
(2021)
Article
Ecology
Nora Junker, Toni Gossmann
Summary: By conducting a phylogeny-based substitution rate analysis of coding genes from seven marmot species, researchers found that sirtuin 1 (SIRT1) has evolved under positive selection in the marmot lineage, potentially contributing to an extended lifespan for marmots.
FRONTIERS IN ECOLOGY AND EVOLUTION
(2021)
Editorial Material
Ecology
Jane M. Waterman, Toni I. Gossmann, Oleg Brandler, John L. Koprowski
FRONTIERS IN ECOLOGY AND EVOLUTION
(2021)
Article
Evolutionary Biology
Toni I. Gossmann, David Waxman
Summary: The article discusses the conditional effect caused by observational thresholds in biology, pointing out the impact on gene frequency trajectories and other areas, especially under purifying selection may lead to significant biases. The study illustrates the measurement of the strength of conditioning and the method of correcting the effect.
GENOME BIOLOGY AND EVOLUTION
(2022)
Article
Evolutionary Biology
David L. J. Vendrami, Toni Gossmann, Nayden Chakarov, Anneke J. Paijmans, Vivienne Litzke, Adam Eyre-Walker, Jaume Forcada, Joseph Hoffman
Summary: Nuclear copies of mitochondrial genes (numts) are common in vertebrate genomes. This study characterizes 25 numts in the Antarctic fur seal genome and identifies two recent numts that have multiple substitutions due to noncanonical insertions.
GENOME BIOLOGY AND EVOLUTION
(2022)
Article
Biology
K. Mavreas, T. I. Gossmann, D. Waxman
Summary: Haldane's analysis on the fixation of beneficial alleles plays a crucial role in population genetic thinking and methods for identifying positive selection; this study expands Haldane's work within a finite-population Wright-Fisher framework; the results have significant implications for population and conservation genetics, providing new avenues for tracing historically beneficial alleles through comparative genomics.