Article
Chemistry, Multidisciplinary
Serafima Guseva, Vincent Schnapka, Wiktor Adamski, Damien Maurin, Rob W. H. Ruigrok, Nicola Salvi, Martin Blackledge
Summary: The liquid-liquid phase separation of flexible biomolecules is a common phenomenon in the formation of membraneless organelles. Nuclear magnetic resonance spectroscopy and molecular dynamics simulations were used to study the dynamics of an intrinsically disordered protein in dilute and dense phases. The results showed that the dynamics of the protein were significantly slowed down and chain-like motions dominated in the dense phase.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Anas Malki, Jean-Marie Teulon, Aldo R. Camacho-Zarco, Shu-Wen W. Chen, Wiktor Adamski, Damien Maurin, Nicola Salvi, Jean-Luc Pellequer, Martin Blackledge
Summary: The study characterizes the conformational and physical behavior of CAHS-8 protein from Hypsibius exemplaris, showing its ability to form fibrous gels that may enhance the protective properties of the proteins. This unique ability of reversible formation of fibrous gels could be associated with the exceptional resistance of tardigrades to harsh stress conditions.
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
Multidisciplinary Sciences
Wenzhe Liu, Limin Chen, Dongbao Yin, Zhiheng Yang, Jianfei Feng, Qi Sun, Luhua Lai, Xuefeng Guo
Summary: This article introduces a single-molecule electrical nanocircuit based on silicon nanowire field-effect transistors (SiNW-FETs), which enables label-free and long-term measurements of intrinsically disordered proteins (IDPs) at the single-molecule level. By studying the interaction of c-Myc with Max and small molecule inhibitors, the self-folding/unfolding process of c-Myc and its interaction mechanism are observed and analyzed in real time. These findings provide a better understanding of the IDP-binding/folding mechanism and offer a promising nanotechnology platform for IDP conformation/interaction studies and drug discovery.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Emery T. Usher, Nafiseh Sabri, Roman Rohac, Amie K. Boal, Tanja Mittag, Scott A. Showalter
Summary: The interaction between Pdx1 and SPOP causes SPOP relocalization from nuclear speckles to the diffuse nucleoplasm, where the ubiquitination activity of Pdx1 mediated by SPOP occurs. Efficient turnover of Pdx1 requires both SB motifs. The subnuclear localization of SPOP-substrate interactions and substrate ubiquitination may be directed by the properties of the substrate itself.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemical Research Methods
Marco Schiavina, Lorenzo Bracaglia, Maria Anna Rodella, Rainer Kuemmerle, Robert Konrat, Isabella Felli, Roberta Pierattelli
Summary: Nuclear magnetic resonance (NMR) spectroscopy is a powerful technique for characterizing biomolecules at atomic resolution. The availability of ultra-high-field NMR instrumentation has opened up new possibilities for studying more complex systems, such as flexible proteins and protein regions. While conducting experiments at such high field strengths comes with challenges, strategies and tricks can be employed to optimize the experiments.
Review
Chemistry, Multidisciplinary
Anton Abyzov, Martin Blackledge, Markus Zweckstetter
Summary: In this review, we discuss the motions of intrinsically disordered proteins inside biomolecular condensates, with a focus on the modulation of motion by liquid-liquid phase separation. We highlight the importance of intermolecular interactions in driving phase separation and influencing biomolecular motions and condensate aging.
Article
Cell Biology
Benjamin Bourgeois, Tianshu Gui, Diana Hoogeboom, Henry G. Hocking, Gesa Richter, Emil Spreitzer, Martin Viertler, Klaus Richter, Tobias Madl, Boudewijn M. T. Burgering
Summary: The study demonstrates how the transcription factor FOXO4 regulates its transcriptional activity through interactions with the structured co-regulator b-catenin, modulated by phosphorylation and other regulatory mechanisms. Additionally, it reveals the role of the b-catenin inhibitor protein ICAT in acting as a molecular switch between anti-proliferative FOXO and pro-proliferative Wnt/TCF/LEF signaling pathways. These findings highlight the importance of intrinsically disordered regions, post-translational modifications, and co-factor binding in regulating transcription factor function.
Article
Chemistry, Multidisciplinary
Samuel Naudi-Fabra, Maud Tengo, Malene Ringkjobing Jensen, Martin Blackledge, Sigrid Milles
Summary: Studying the conformational landscape of intrinsically disordered and partially folded proteins is challenging and requires an integrated approach using multiple techniques to accurately describe the conformational ensembles of these proteins. This integrated approach has been successfully tested and validated, providing new insights into the conformational landscape of viral proteins and demonstrating its potential for integrative dynamic structural biology.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Biochemistry & Molecular Biology
Jaka Kragelj, Rania Dumarieh, Yiling Xiao, Kendra K. K. Frederick
Summary: Frozen proteins at cryogenic temperatures can provide detailed conformational restraints for DNP MAS NMR studies. Using peak shapes, conformational features of individual conformers in the ensemble can be assigned through simulation. This has important implications for studying proteins with intrinsically disordered regions in living cells.
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
Biochemistry & Molecular Biology
Samuel Naudi-Fabra, Martin Blackledge, Sigrid Milles
Summary: Single molecule fluorescence and nuclear magnetic resonance spectroscopy are powerful techniques for analyzing intrinsically disordered proteins. They provide complementary views to decipher the complex properties and interactions of IDPs, and have made significant contributions to our understanding of their molecular characteristics.
Article
Biochemistry & Molecular Biology
Fanni Sebak, Janos Szolomajer, Nandor Papp, Gabor K. Toth, Andrea Bodor
Summary: The type of neighboring amino acids, especially aromatic and positively charged sidechains, has been found to affect the cis-Pro content. These findings can assist in the design of protein regions with specific cis-Pro content and contribute to a better understanding of the roles and functions of IDPs.
FRONTIERS IN BIOSCIENCE-LANDMARK
(2023)
Article
Biochemical Research Methods
Jhullian J. Alston, Andrea Soranno, Alex S. Holehouse
Summary: Over the past two decades, intrinsically disordered proteins and protein regions have been recognized as essential drivers of cellular function, with singlemolecule fluorescence spectroscopy and molecular simulations providing insight into their behavior. When combined, these techniques offer complementary information that can help uncover complex molecular details.
Article
Chemistry, Physical
Souvik Dey, Matthew MacAinsh, Huan-Xiang Zhou
Summary: For intrinsically disordered proteins (IDPs), the dynamics of the backbone play a key role in encoding their function. The dynamics are regulated by local interactions, secondary structures, and glycines. These sequence-dependent changes in backbone dynamics allow IDPs to respond to binding partners in a versatile manner.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2022)
Article
Multidisciplinary Sciences
Kalle H. Sipila, Vipin Ranga, Pekka Rappu, Markku Mali, Laura Pirila, Ilona Heino, Johanna Jokinen, Jarmo Kapyla, Mark S. Johnson, Jyrki Heino
SCIENTIFIC REPORTS
(2017)
Article
Biochemistry & Molecular Biology
Kalle H. Sipila, Kati Drushinin, Pekka Rappu, Johanna Jokinen, Tiina A. Salminen, Antti M. Salo, Jarmo Kapyla, Johanna Myllyharju, Jyrki Heino
JOURNAL OF BIOLOGICAL CHEMISTRY
(2018)
Article
Endocrinology & Metabolism
Marjaana Ojalill, Pekka Rappu, Elina Siljamaki, Pekka Taimen, Peter Bostrom, Jyrki Heino
Article
Multidisciplinary Sciences
Maria Salmela, Johanna Jokinen, Silja Tiitta, Pekka Rappu, R. Holland Cheng, Jyrki Heino
SCIENTIFIC REPORTS
(2017)
Letter
Gastroenterology & Hepatology
Joeri Tulkens, Glenn Vergauwen, Jan Van Deun, Edward Geeurickx, Bert Dhondt, Lien Lippens, Marie-Angelique De Scheerder, Ilkka Miinalainen, Pekka Rappu, Bruno G. De Geest, Katrien Vandecasteele, Debby Laukens, Linos Vandekerckhove, Hannelore Denys, Jo Vandesompele, Olivier De Wever, An Hendrix
Review
Biochemistry & Molecular Biology
Pekka Rappu, Antti M. Salo, Johanna Myllyharju, Jyrki Heino
EXTRACELLULAR MATRIX
(2019)
Article
Biology
Carlos J. Diaz Osterman, Duygu Ozmadenci, Elizabeth G. Kleinschmidt, Kristin N. Taylor, Allison M. Barrie, Shulin Jiang, Lisa M. Bean, Florian J. Sulzmaier, Christine Jean, Isabelle Tancioni, Kristen Anderson, Sean Uryu, Edward A. Cordasco, Jian Li, Xiao Lei Chen, Guo Fu, Marjaana Ojalill, Pekka Rappu, Jyrki Heino, Adam M. Mark, Guorong Xu, Kathleen M. Fisch, Vihren N. Kolev, David T. Weaver, Jonathan A. Pachter, Balazs Gyorffy, Michael T. McHale, Denise C. Connolly, Alfredo Molinolo, Dwayne G. Stupack, David D. Schlaepfer
Article
Biochemistry & Molecular Biology
Elina Siljamaki, Pekka Rappu, Pilvi Riihila, Liisa Nissinen, Veli-Matti Kahari, Jyrki Heino
Article
Endocrinology & Metabolism
Marjaana Ojalill, Noora Virtanen, Pekka Rappu, Elina Siljamaki, Pekka Taimen, Jyrki Heino
Article
Cell Biology
Jan Van Deun, Quentin Roux, Sarah Deville, Thibaut Van Acker, Pekka Rappu, Ilkka Miinalainen, Jyrki Heino, Frank Vanhaecke, Bruno G. De Geest, Olivier De Wever, An Hendrix
Article
Biochemical Research Methods
Edward Geeurickx, Lien Lippens, Pekka Rappu, Bruno G. De Geest, Olivier De Wever, An Hendrix
Summary: This study presents a protocol for using recombinant EV as a biological reference material to evaluate EV application performance, map technical variability, and promote inter-laboratory studies, which can be completed in about 4-5 days.
Article
Oncology
Pekka Rappu, Ujjwal Suwal, Elina Siljamaki, Jyrki Heino
Summary: It has been discovered that the citrullination of matrisome proteins occurs in human cancers, with variations between different tumors. Fibrinogen and fibronectin are the most frequently citrullinated proteins, which are typically associated with inflammation. Further analysis using three-dimensional cell cocultures suggests that cancer cells and fibroblasts cannot citrullinate matrisome proteins in the tumor stroma, and the citrullination of matrisome proteins may be protected in spheroid cultures.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Sofie Van Dorpe, Lien Lippens, Robin Boiy, Claudio Pinheiro, Glenn Vergauwen, Pekka Rappu, Ilkka Miinalainen, Philippe Tummers, Hannelore Denys, Olivier De Wever, An Hendrix
Summary: In this study, an automated liquid handling workstation was developed for the density-based separation of extracellular vesicles (EV) from human body fluids. The performance of the automated method was compared to manual handling by experienced or inexperienced researchers. The results showed that the automated EV separation method significantly reduced the variability in EV recovery and exhibited high reproducibility, specificity, and reduced hands-on time.
JOURNAL OF NANOBIOTECHNOLOGY
(2023)
Article
Cell Biology
Bert Dhondt, Claudio Pinheiro, Edward Geeurickx, Joeri Tulkens, Glenn Vergauwen, Edwin van der Pol, Rienk Nieuwland, Anneleen Decock, Ilkka Miinalainen, Pekka Rappu, Gary Schroth, Scott Kuersten, Jo Vandesompele, Pieter Mestdagh, Nicolaas Lumen, Olivier De Wever, An Hendrix
Summary: The analysis of extracellular vesicles (EV) in blood samples is being extensively studied, as it has the potential to provide clinically meaningful biomarkers for health and disease. This study investigated the impact of different blood collection tubes and processing intervals on EV characteristics in blood samples. The results showed that the choice of blood collection tube and processing interval significantly affected various metrics related to blood sample quality, ex-vivo generation of EV from blood cells, EV recovery, and molecular signatures associated with EV. These findings provide valuable guidance for selecting optimal conditions for EV analysis and contribute to standardizing EV studies.
JOURNAL OF EXTRACELLULAR VESICLES
(2023)
Article
Cell Biology
Bert Dhondt, Edward Geeurickx, Joeri Tulkens, Jan Van Deun, Glenn Vergauwen, Lien Lippens, Ilkka Miinalainen, Pekka Rappu, Jyrki Heino, Piet Ost, Nicolaas Lumen, Olivier De Wever, An Hendrix
JOURNAL OF EXTRACELLULAR VESICLES
(2020)
