Review
Biochemistry & Molecular Biology
Judit Olah, Tibor Szenasi, Attila Lehotzky, Victor Norris, Judit Ovadi
Summary: Protein-protein interactions (PPIs) play a crucial role in fundamental processes and are associated with pathological conditions. However, discovering drugs that can modulate PPIs poses challenges and limitations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(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)
Review
Biochemistry & Molecular Biology
Ugo Dionne, Lily J. Percival, Francois J. M. Chartier, Christian R. Landry, Nicolas Bisson
Summary: The assembly of complexes following the detection of extracellular signals is controlled by signaling proteins with multiple peptide binding modules. The SH3 family, with around 300 annotated SH3 domains in humans, is a modular protein interaction module that regulates various signaling processes. Recent findings have challenged the simple model of SH3 domains as portable domains binding to specific proline-rich peptide motifs, by revealing their allosteric contributions in the host protein context, phosphoregulation, and roles in phase separation.
TRENDS IN BIOCHEMICAL SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Aakriti Upadhyay, Chinwe Ekenna
Summary: Understanding the binding behavior and conformational dynamics of intrinsically disordered proteins (IDPs) is crucial. We proposed an algorithm that explores IDP binding behavior with protein complexes by extracting topological and geometric features from the protein surface model. Our method outperformed the compared methods in computation performance and binding affinity in experimental conformations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
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
Chemistry, Multidisciplinary
Yang Lu, Zi-Di Yu, Hio-Ieng Un, Ze-Fan Yao, Hao-Yang You, Wenlong Jin, Liang Li, Zi-Yuan Wang, Bo-Wei Dong, Stephen Barlow, Elena Longhi, Chong-an Di, Daoben Zhu, Jie-Yu Wang, Carlos Silva, Seth R. Marder, Jian Pei
Summary: A simple solution-based co-deposition method has been reported to achieve high conductivity n-doped polymers. These polymers exhibit surprising structural tolerance and excellent miscibility with commonly used n-dopants, allowing high concentrations and high mobility of charge carriers simultaneously, resulting in excellent electrical conductivity and thermoelectric performance.
ADVANCED MATERIALS
(2021)
Article
Biochemistry & Molecular Biology
Romana T. Pop, Alessandra Pisante, Dorka Nagy, Patrick C. N. Martin, Liudmila A. Mikheeva, Ateequllah Hayat, Gabriella Ficz, Nicolae Radu Zabet
Summary: Transcription factors (TFs) are proteins that regulate gene expression by specifically binding to DNA regulatory regions. This study used ChIP-seq data and an explainable statistical model called ChIPanalyser to investigate the binding mechanism of hundreds of TFs. The results showed that approximately one third of TFs are predicted to bind the genome in a DNA accessibility independent manner, including TFs that can open chromatin and TFs with similar binding motifs. The study demonstrated the high accuracy of ChIPanalyser in predicting the binding of TFs and revealed the ability of many TFs to bind dense chromatin.
NUCLEIC ACIDS RESEARCH
(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)
Article
Biochemistry & Molecular Biology
Rajesh Jaiprashad, Sachith Roch De Silva, Lisette M. Fred M. Lucena, Ella Meyer, Steven J. Metallo
Summary: Intrinsically disordered proteins (IDPs) play important roles in both normal and disease states, and small molecules can target the disordered regions for therapeutic purposes. This study demonstrates the portability of a minimal small-molecule binding sequence in different IDP contexts, as well as the opposing effects of flanking residues on small-molecule binding. These findings shed light on the modular nature of small-molecule binding sites in IDPs.
Article
Biochemistry & Molecular Biology
Angelita Rebollo, Eric Savier, Pierre Tuffery
Summary: PEPscan is an effective method for identifying interfering peptides, which can interfere with protein-protein interactions. It is able to rapidly and accurately identify specific interfering peptides, but further validation is needed regarding their location at the protein-protein interface.
Article
Biochemistry & Molecular Biology
Hao Wu, Yamini Dalal, Garegin A. Papoian
Summary: Linker histone H1 is crucial for chromatin packaging and gene expression, with dysregulation commonly seen in tumor cells. It alters chromatin condensation levels by binding to multiple sites on nucleosomal particles. The disordered domains of H1 enhance binding affinity and restrict dynamics, ultimately modulating nucleosome structure and dynamics.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Zhongli Chen, Biting Liang, Yingfu Wu, Quanzhong Liu, Hongming Zhang, Hao Wu
Summary: This study proposes a network-based method (Netkmeans) for accurately and effectively detecting dysregulated modules in cancer. By constructing a gene network and a comprehensive evaluation function, this method outperforms other methods in terms of statistical significance and biological relevance. Experimental results demonstrate the importance of the dysregulated modules detected by Netkmeans in the development and treatment of cancer.
BRIEFINGS IN FUNCTIONAL GENOMICS
(2022)
Review
Biochemistry & Molecular Biology
Ranran Chen, Xinlu Li, Yaqing Yang, Xixi Song, Cheng Wang, Dongdong Qiao
Summary: This paper presents a comprehensive overview of recently published predictors for intrinsically disordered protein (IDP) binding site prediction. The authors collected 30 representative predictors and summarized their databases, features, and algorithms. The predictors were divided into scoring functions, machine learning-based prediction, and consensus approaches, with detailed descriptions of their algorithms and performances. This study not only provides a full picture of the current status of IDP binding prediction, but also serves as a guide for selecting different methods and inspires future development trends and principles.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Genetics & Heredity
Yanchao Wang, Wenjun Zhou, Yan Chen, Dong He, Zhen Qin, Zhao Wang, Song Liu, Lei Zhou, Jianwen Su, Chi Zhang
Summary: Osteoarthritis is a global cause of pain, disability, and social burden in the elderly, and its etiology and molecular mechanism are still unclear. This study identified potential hub genes associated with osteoarthritis through weighted gene co-expression network analysis, and confirmed their upregulation in patients with OA. Additionally, a predictive model for OA risk was developed.
FRONTIERS IN GENETICS
(2022)
Article
Chemistry, Multidisciplinary
Giovanna Viola, Carlo Giorgio Barracchia, Roberto Tira, Francesca Parolini, Giulia Leo, Massimo Bellanda, Francesca Munari, Stefano Capaldi, Mariapina D'Onofrio, Michael Assfalg
Summary: Understanding the interactions between nanoparticles and proteins is crucial for their successful application in biology. This study reveals a new type of nano-bio interaction, where ultrasmall gold nanoparticles form stable multimolecular assemblies with intrinsically disordered proteins. This finding has important implications for the targeting of aberrant protein aggregation in cells.
Article
Genetics & Heredity
Benjamin Z. Stanton, Courtney Hodges, Joseph P. Calarco, Simon M. G. Braun, Wai Lim Ku, Cigall Kadoch, Keji Zhao, Gerald R. Crabtree
Article
Medicine, Research & Experimental
Courtney Hodges, Jacob G. Kirkland, Gerald R. Crabtree
COLD SPRING HARBOR PERSPECTIVES IN MEDICINE
(2016)
Article
Biochemistry & Molecular Biology
H. Courtney Hodges, Benjamin Z. Stanton, Katerina Cermakova, Chiung-Ying Chang, Erik L. Miller, Jacob G. Kirkland, Wai Lim Ku, Vaclav Veverka, Keji Zhao, Gerald R. Crabtree
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2018)
Article
Biochemistry & Molecular Biology
Erik L. Miller, Diana C. Hargreaves, Cigall Kadoch, Chiung-Ying Chang, Joseph P. Calarco, Courtney Hodges, Jason D. Buenrostro, Kairong Cui, William J. Greenleaf, Keji Zhao, Gerald R. Crabtree
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2017)
Article
Biochemistry & Molecular Biology
H. Courtney Hodges, Benjamin Z. Stanton, Katerina Cermakova, Chiung-Ying Chang, Erik L. Miller, Jacob G. Kirkland, Wai Lim Ku, Vaclav Veverka, Keji Zhao, Gerald R. Crabtree
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2018)
Article
Biochemistry & Molecular Biology
Erik L. Miller, Diana C. Hargreaves, Cigall Kadoch, Chiung-Ying Chang, Joseph P. Calarco, Courtney Hodges, Jason D. Buenrostro, Kairong Cui, William J. Greenleaf, Keji Zhao, Gerald R. Crabtree
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2017)
Article
Multidisciplinary Sciences
Subhalakshmi Sharma, Katerina Cermakova, Jan De Rijck, Jonas Demeulemeester, Milan Fabry, Sara El Ashkar, Siska Van Belle, Martin Lepsik, Petr Tesina, Vojtech Duchoslav, Petr Novak, Martin Hubalek, Pavel Srb, Frauke Christ, Pavlina Rezacova, H. Courtney Hodges, Zeger Debyser, Vaclav Veverka
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2018)
Review
Biochemistry & Molecular Biology
Katerina Cermakova, H. Courtney Hodges
Article
Genetics & Heredity
Cigall Kadoch, Diana C. Hargreaves, Courtney Hodges, Laura Elias, Lena Ho, Jeff Ranish, Gerald R. Crabtree
Article
Multidisciplinary Sciences
Jeneffer P. England, Yuxin Hao, Lihui Bai, Virginia Glick, H. Courtney Hodges, Susan S. Taylor, Rodrigo A. Maillard
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2018)
Article
Multidisciplinary Sciences
Yuxin Hao, Jeneffer P. England, Luca Bellucci, Emanuele Paci, H. Courtney Hodges, Susan S. Taylor, Rodrigo A. Maillard
NATURE COMMUNICATIONS
(2019)
Article
Oncology
Deborah R. Surman, Yuan Xu, Min-Jung Lee, Jane Trepel, Kate Brown, Maheshwari Ramineni, Taylor G. Splawn, Laurence P. Diggs, H. Courtney Hodges, Jeremy L. Davis, Hyun-Sung Lee, Bryan M. Burt, Robert Taylor Ripley
Summary: Approximately 20,000 patients are diagnosed with esophageal adenocarcinoma and malignant pleural mesothelioma each year, with fewer than 20% surviving 5 years. Targeting mitochondrial proteins through dynamic Bcl-2 homology-3 profiling can enhance the efficacy of combinatorial therapy in these patients with multiple mutations contributing to tumor development.
MOLECULAR CANCER THERAPEUTICS
(2021)
Review
Biochemistry & Molecular Biology
Katerina Cermakova, Vaclav Veverka, H. Courtney Hodges
Summary: Interaction scaffolds selectively recognize disordered proteins, shaping protein interactomes. One important scaffold, the TFIIS N-terminal domain (TND), contributes to transcription by selectively reading intrinsically disordered sequences of other proteins. This review explores the structural and functional properties of TNDs and their ligands, known as TND-interacting motifs (TIMs), and discusses their involvement in transcriptional regulation. The TND interactome, enriched among transcription elongation regulators, plays widespread roles in the regulation of transcriptional processes.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2023)
Review
Oncology
Eric A. Smith, H. Courtney Hodges