Article
Chemistry, Multidisciplinary
Valentin Bauer, Boris Schmidtgall, Gergo Gogl, Jozica Dolenc, Judit Osz, Yves Nomine, Camille Kostmann, Alexandra Cousido-Siah, Andre Mitschler, Natacha Rochel, Gilles Trave, Bruno Kieffer, Vladimir Torbeev
Summary: This study utilized a specific amino acid substitution pattern to modify the free activation domain of transcriptional coactivator ACTR, resulting in increased binding affinity to CREB-binding protein. The X-ray structure of the modified ACTR domain - NCBD complex revealed a unique conformation of ACTR, demonstrating a strategy for characterizing individual conformational states of IDPs.
Article
Biochemistry & Molecular Biology
Nicolas Palopoli, Julia Marchetti, Alexander M. Monzon, Diego J. Zea, Silvio C. E. Tosatto, Maria S. Fornasari, Gustavo Parisi
Summary: This study reveals that intrinsically disordered proteins (IDPs) evolve under strong site-specific evolutionary rate heterogeneity, mainly due to different constraints from their inter-residue contacts. Evolutionary rate profiles correlate with the experimentally observed conformational diversity, allowing the description of different conformational patterns possibly related to their structure-function relationships.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Virology
Satyamurthy Kundharapu, Tirumala Kumar Chowdary
Summary: Dengue virus replication relies on interactions between NS proteins, with the NS4b-NS3 interaction enhancing helicase activity. The N-terminal region of NS4b interacts with NS3, wrapping around the C-terminal subdomain of the helicase and influencing its activity.
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
Xi Wang, Harry M. Greenblatt, Lavi S. Bigman, Binhan Yu, Channing C. Pletka, Yaakov Levy, Junji Iwahara
Summary: This study investigates how D/E repeats cause autoinhibition of HMGB1 and its specific binding to cisplatin-modified DNA. By varying ionic strength, the conformational equilibrium between autoinhibited and uninhibited states can be shifted, revealing fuzzy interactions of D/E repeats with other intrinsically disordered regions. Mutations mimicking post-translational modifications relevant to nuclear export of HMGB1 can moderately modulate DNA-binding affinity, possibly by impacting the autoinhibition.
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)
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
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
Biochemistry & Molecular Biology
Christopher J. Brown, Chandra S. Verma, David P. Lane, Dilraj Lama
Summary: A study was conducted to develop peptide derivatives from intrinsically disordered eIF4G scaffold through molecular dynamics simulations and biophysical assays for regulating eIF4E protein interactions. Insights into the differential binding affinities of these peptides and the rate-limiting Y4: P38 hydrogen-bond interaction between the peptide and eIF4E were key findings. These insights were used to design features into the peptide to generate a potent eIF4E binder for potential therapeutic interventions in oncology.
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2021)
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
Vladimir D. Manyilov, Nikolay S. Ilyinsky, Semen V. Nesterov, Baraa M. G. A. Saqr, Guy W. Dayhoff, Egor V. Zinovev, Simon S. Matrenok, Alexander V. Fonin, Irina M. Kuznetsova, Konstantin K. Turoverov, Valentin Ivanovich, Vladimir N. Uversky
Summary: This article examines the impact of intrinsically disordered proteins and regions on aging-related processes. The findings indicate that these disordered components play significant roles in aging, particularly in genome regulation.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Review
Chemistry, Multidisciplinary
Debapriya Das, Samrat Mukhopadhyay
Summary: Protein folding and dynamics are influenced by both thermal and viscosity effects, including external viscous drag from solvent molecules and internal friction within the polypeptide chain. The physical origin of internal friction in intrinsically disordered proteins remains unclear, with diffusive conformational dynamics dominated by segmental motion of the backbone. Polymer models with internal friction are used to describe the friction in complex biopolymeric systems such as intrinsically disordered proteins.
ACCOUNTS OF CHEMICAL RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Lynn G. Schrag, Xiaorong Liu, Indhujah Thevarajan, Om Prakash, Michal Zolkiewski, Jianhan Chen
Summary: Intrinsically disordered proteins play crucial roles in cell decision making and regulatory networks; cancer-associated mutations in p53-TAD can significantly disrupt the balance of interactions with regulatory proteins; these mutations may modulate the disordered state of p53-TAD to perturb interactions with regulators.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
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)
Article
Biochemical Research Methods
Noriyuki Kodera, Toshio Ando
Summary: Intrinsically disordered proteins (IDPs) are proteins that are partially or entirely disordered, and their intrinsically disordered regions (IDRs) explore a wide range of structural space due to their highly flexible nature. Conventional structural analyses are not suitable for studying the dynamic structure of IDPs, so single-molecule measurement tools are needed. High-speed atomic force microscopy (HS-AFM) is a unique tool that allows direct visualization of the shape and motion of individual biomolecules under near physiological conditions, without any chemical labeling.
Article
Biophysics
Glauce M. Barbosa, Maria A. Morando, Andrea T. Da Poian, Fabio C. L. Almeida
Summary: Dengue virus, an enveloped virus belonging to the Flaviviridae family, is responsible for an endemic arboviral disease in humans. The capsid protein of Dengue virus forms homodimers in solution, consisting of 4 alpha-helices and an intrinsically disordered N-terminal region. The N-terminal region is involved in binding membranous structures in host cells and nucleotide recognition.
BIOMOLECULAR NMR ASSIGNMENTS
(2023)
Article
Biochemistry & Molecular Biology
Victor David, Luciana Serrao Wermelinger, Flavia Serra Frattani, Antonio Gilcler Ferreira Lima, Yasmyn Fernandes Silva Santos, Paulo Antonio de Souza Mourao, Fabio Ceneviva Lacerda Almeida, Eleonora Kurtenbach, Russolina Benedeta Zingali
Summary: This study expresses and analyzes the rJararacin protein, which has been found to effectively inhibit the adhesion of B16F10 cells and platelets to the fibronectin matrix, and inhibit platelet aggregation induced by ADP, collagen, and thrombin. Furthermore, rJararacin can effectively prevent platelet aggregation and thrombus formation in vitro and in vivo. These results suggest that rJararacin has the potential as an αIIbβ3 antagonist to prevent arterial thrombosis.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2023)
Article
Biophysics
Karina C. Pougy, Gilberto Sachetto-Martins, Fabio C. L. Almeida, Anderson S. Pinheiro
Summary: AtGRP2 is a 19-kDa RNA-binding glycine-rich protein that regulates key processes in A. thaliana, including flowering time and cold adaptation. It is preferentially expressed in developing tissues and is highly induced by cold and abiotic stresses. AtGRP2 is involved in the development of embryos and seeds, and promotes DNA/RNA denaturation during cold acclimation.
BIOMOLECULAR NMR ASSIGNMENTS
(2023)
Editorial Material
Biochemistry & Molecular Biology
Sonia Goncalves, Nuno C. Santos
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Fabricia L. Fontes-Dantas, Gabriel G. Fernandes, Elisa G. Gutman, Emanuelle V. De Lima, Leticia S. Antonio, Mariana B. Hammerle, Hannah P. Mota-Araujo, Lilian C. Colodeti, Suzana M. B. Araujo, Gabrielle M. Froz, Talita N. da Silva, Larissa A. Duarte, Andreza L. Salvio, Karina L. Pires, Luciane A. A. Leon, Claudia Cristina F. Vasconcelos, Luciana Romao, Luiz Eduardo B. Savio, Jerson L. Silva, Robson da Costa, Julia R. Clarke, Andrea T. Da Poian, Soniza V. Alves-Leon, Giselle F. Passos, Claudia P. Figueiredo
Summary: Cognitive dysfunction in post-COVID-19 syndrome may be caused by the release of SARS-CoV-2 Spike protein, which can lead to neuroinflammation, synapse elimination, and memory dysfunction mediated by Toll-like receptor 4 (TLR4) signaling. Infusing Spike protein into the brains of mice reproduced cognitive impairment similar to post-COVID-19 syndrome. In a group of 86 mild COVID-19 patients, a specific TLR4 genotype was associated with poor cognitive outcome. These findings highlight TLR4 as a key target for investigating long-term cognitive dysfunction after COVID-19 infection.
Article
Multidisciplinary Sciences
Thais C. Neves-Martins, Nathane C. Mebus-Antunes, Carlos H. G. Neto, Glauce M. Barbosa, Fabio C. L. Almeida, Icaro P. Caruso, Andrea T. Da Poian
Summary: The researchers designed a mutant of the dengue virus capsid protein (DENVC) by replacing a positively charged spot with a cysteine residue, resulting in the self-assembly of capsid-like particles (CLP) in solution without nucleic acids.
Article
Biology
Catarina S. Lopes, Juliana Curty, Filomena A. Carvalho, A. Hernandez-Machado, Koji Kinoshita, Nuno C. Santos, Rui D. M. Travasso
Summary: This study measured the adhesion between human erythrocytes using atomic force microscopy (AFM) and observed its effect using micropipette aspiration technique, in the presence and absence of fibrinogen. A mathematical model was developed based on experimental data to study erythrocyte-erythrocyte adhesion forces and changes in erythrocyte morphology. The presence of fibrinogen increased the work and detachment force required to overcome the adhesion between erythrocytes. The mathematical simulation successfully tracked the changes in erythrocyte morphology and cell-cell adhesion.
COMMUNICATIONS BIOLOGY
(2023)
Article
Behavioral Sciences
Isis N. O. Souza, Brenda S. Andrade, Paula S. Frost, Romulo L. S. Neris, Daniel Gavino-Leopoldino, Andrea T. Da Poian, Iranaia Assuncao-Miranda, Claudia P. Figueiredo, Julia R. Clarke, Gilda A. Neves
Summary: In this study, different outcomes were observed in mice infected with Zika virus (ZIKV) based on age and sex: neonatally infected animals showed an increase in prepulse inhibition (PPI) and delayed startle latency, while adult-infected male mice had lower startle amplitude and both sexes showed PPI impairment 14 days after infection. These findings contribute to a better understanding of the functional impacts of ZIKV on the nervous system and provide insight into the behavioral and cognitive alterations caused by the virus. The study supports the use of startle reflex testing in ZIKV-exposed patients, especially infants, for early detection of functional neuromotor damage and early intervention.
BEHAVIOURAL BRAIN RESEARCH
(2023)
Article
Infectious Diseases
Katia Maria dos Santos Cabral, Ramon Cid Gismonti Baptista, Terezinha Marta Pereira Pinto Castineiras, Amilcar Tanuri, Fabiana Avila Carneiro, Marcius da Silva Almeida, Monica Montero-Lomeli
Summary: The SARS-CoV-2 pandemic called for rapid diagnosis of COVID-19 cases to prevent disease transmission. This study validates the use of RT-LAMP in saliva samples and demonstrates high accuracy in purified RNA-saliva samples. Despite mass vaccination, the presence of new strains and slow progress in vaccinations contribute to the spread of COVID-19. This study shows that tracking new COVID-19 cases in a large population is feasible using raw saliva samples in the RT-LAMP assay, which provides accurate results and a less invasive testing option.
BRAZILIAN JOURNAL OF INFECTIOUS DISEASES
(2023)
Article
Biochemistry & Molecular Biology
Priscilla L. S. Boon, Ana S. Martins, Xin Ni Lim, Francisco J. Enguita, Nuno C. Santos, Peter J. Bond, Yue Wan, Ivo C. Martins, Roland G. Huber
Summary: Dengue virus is a significant health risk in tropical and subtropical regions. The structure of the packaged genome in complex with C proteins remains elusive. This study investigates the interactions of C proteins with viral RNA and shows their role in coordinating key interactions for proper packaging of viral RNA.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Maria Carvalho, Marcia M. Medeiros, Ines Morais, Catarina S. Lopes, Ana Balau, Nuno C. Santos, Filomena A. Carvalho, Ana Paula Arez
Summary: Malaria is a major global public health problem that contributes to poverty and inequality. Pyruvate kinase deficiency, which leads to an increased concentration of 2,3-diphosphoglycerate (2,3-DPG), has been associated with resistance to malaria. This study investigates the effects of 2,3-DPG on the morphology, biomechanical properties, and membrane of red blood cells infected with Plasmodium falciparum.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Parasitology
Suelen Silva Gomes Dias, Tamires Cunha-Fernandes, Vinicius Cardoso Soares, Cecilia J. G. de Almeida, Patricia T. Bozza
Summary: Lipid droplets (LD) play important roles in cell metabolism, immune response, neurodevelopment, and neurodegenerative diseases. Recent studies have shown that LD are involved in Zika virus replication and pathogenesis, and targeting lipid metabolism and LD biogenesis may represent potential strategies for anti-Zika virus treatment.
MEMORIAS DO INSTITUTO OSWALDO CRUZ
(2023)
