Article
Multidisciplinary Sciences
Yuko Hasegawa, Kevin Struhl
Summary: The transcription factor SP1 exhibits varying binding dynamics at different target sites in the human genome, potentially influenced by factors such as location and cobinding factors.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Biochemistry & Molecular Biology
Kangwen Xu, Long Lin, Danyu Shen, Shan-Ho Chou, Guoliang Qian
Summary: The review summarizes the mechanisms through which Clp, a CRP-like protein, initiates a mobile-attack strategy in Lysobacter enzymogenes against fungal pathogens, including binding to DNA in a unique pattern, interacting directly with small molecules or responding to them, and specific interactions with proteins adopting distinct structures.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Article
Cell Biology
Luqian Zheng, Jingjing Liu, Lijie Niu, Mohammad Kamran, Ally W. H. Yang, Arttu Jolma, Qi Dai, Timothy R. Hughes, Dinshaw J. Patel, Long Zhang, Supriya G. Prasanth, Yang Yu, Aiming Ren, Eric C. Lai
Summary: In this study, the researchers investigated how BEN factors identify their targets in humans by characterizing several mammalian BEN domain factors. They provided structural insights into sequence-specific DNA binding by these BEN proteins. The findings expand the understanding of BEN factors' DNA recognition activities and shed light on the mechanism of sequence-specific DNA binding by mammalian BEN proteins.
GENES & DEVELOPMENT
(2022)
Article
Multidisciplinary Sciences
You Li, Zhiqiang Li, Ruiling Chen, Min Lian, Hanxiao Wang, Yiran Wei, Zhengrui You, Jun Zhang, Bo Li, Yikang Li, Bingyuan Huang, Yong Chen, Qiaoyan Liu, Zhuwan Lyu, Xueying Liang, Qi Miao, Xiao Xiao, Qixia Wang, Jingyuan Fang, YongYong Shi, Xiangdong Liu, Michael F. Seldin, M. Eric Gershwin, Ruqi Tang, Xiong Ma
Summary: Genome-wide association studies have identified a genetic locus, 19p13.3, associated with primary biliary cholangitis (PBC). Through functional annotations and experimental validations, the study suggests that a specific variant, rs2238574, may regulate the expression of ARID3A and affect the severity of PBC.
NATURE COMMUNICATIONS
(2023)
Review
Plant Sciences
Lucia Strader, Dolf Weijers, Doris Wagner
Summary: This article reviews new findings on the function of plant transcription factors and their role in shaping transcription in the context of chromatin.
CURRENT OPINION IN PLANT BIOLOGY
(2022)
Article
Microbiology
Yizhao Luan, Zehua Tang, Yao He, Zhi Xie
Summary: In this study, evidence was provided showing that coevolving residues in TF domains contribute to DNA binding specificity. It was demonstrated that the coevolving residues are more likely to coevolve with other TF subclass-determining sites and mutation of these coevolving residues could significantly reduce the stability of the TF-DNA complex. Overall, this study expands our understanding of the interaction among coevolving residues in TFs and their importance in transcriptional regulation.
MICROBIOLOGY SPECTRUM
(2023)
Article
Multidisciplinary Sciences
Zachery Mielko, Yuning Zhang, Harshit Sahay, Yiling Liu, Matthew A. Schaich, Brittani Schnable, Abigail M. Morrison, Debbie Burdinski, Sheera Adar, Miles Pufall, Bennett Van Houten, Raluca Gordan, Ariel Afek
Summary: Somatic mutations are highly concentrated at transcription factor binding sites, particularly in melanomas with UV-induced mutations. The inefficient repair of UV lesions within TF-binding sites is proposed as one of the main mechanisms for this hypermutation pattern due to competition between TFs and DNA repair proteins. However, the impact of UV irradiation on TF binding to DNA and whether TFs maintain specificity for their DNA sites after UV exposure remain unclear. Using a high-throughput approach called UV-Bind, researchers found that UV lesions significantly altered the DNA binding preferences of all tested TFs, with a decrease in binding specificity. Despite the overall reduction in DNA-binding specificity, TFs can still compete with repair proteins for lesion recognition, consistent with their specificity for UV-irradiated DNA.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemical Research Methods
Manuel Tognon, Vincenzo Bonnici, Erik Garrison, Rosalba Giugno, Luca Pinello
Summary: GRAFIMO is a command-line tool for scanning known TF DNA motifs in VGs, extending the standard PWM scanning procedure by considering variations and alternative haplotypes encoded in a VG, recovering additional potential binding sites than scanning only the reference genome.
PLOS COMPUTATIONAL BIOLOGY
(2021)
Article
Chemistry, Analytical
Bingzhi Li, Bin Zhou, Yue Chen, Xing Zhang, He Huang
Summary: In this study, a new strategy was proposed to sensitively detect transcription factors using T4 DNA ligase protection assay and rolling circle amplification. By preventing the ligation reaction through the binding of T4 DNA ligase to the nick region of dsDNA, the undesired dissociation of TF-DNA complexes was effectively avoided, improving the accuracy of the assay. Through sequence engineering, multiple transcription factors can be detected at low picomolar levels.
SENSORS AND ACTUATORS B-CHEMICAL
(2022)
Article
Computer Science, Artificial Intelligence
Shushan Toneyan, Ziqi Tang, Peter K. Koo
Summary: This study introduces a unified evaluation framework and uses it to compare different binary and quantitative models for predicting chromatin accessibility data. The results show that quantitative modeling improves the generalizability and interpretability of the models, and a robustness metric is introduced to enhance model selection and variant effect predictions.
NATURE MACHINE INTELLIGENCE
(2022)
Article
Biochemistry & Molecular Biology
Matthew Dyer, Quy Xiao Xuan Lin, Sofiia Shapoval, Denis Thieffry, Touati Benoukraf
Summary: MethMotif is a publicly available database that provides a comprehensive repository of transcription factor-binding profiles with DNA methylation patterns. The latest release includes over 700 position weight matrices, segregated based on their cofactors and DNA methylation status. The database also offers precomputed GO annotations for human TFs and TF-co-TF complexes, allowing for a comprehensive analysis of TF functions in their context with cofactors. Furthermore, MethMotif has been expanded to include data for two additional species, increasing its applicability and value to the scientific community.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemical Research Methods
Zhihua Du, Tianyou Huang, Vladimir N. Uversky, Jianqiang Li
Summary: Transcription factors (TFs) are DNA binding proteins that regulate gene expression by binding to specific DNA sequences. While experimental methods for identifying TFs are time-consuming and costly, computational methods have been developed to overcome these limitations. However, the predictive performance of these tools can be further improved in terms of accuracy.
IEEE-ACM TRANSACTIONS ON COMPUTATIONAL BIOLOGY AND BIOINFORMATICS
(2023)
Article
Multidisciplinary Sciences
Pengcheng Zhang, Haochen Wang, Hanwen Xu, Lei Wei, Liyang Liu, Zhirui Hu, Xiaowo Wang
Summary: Designing promoters with desirable properties is crucial in synthetic biology. DeepSEED, an AI-aided framework that combines expert knowledge with deep learning techniques, has been successful in efficiently designing synthetic promoters and capturing implicit features in flanking sequences.
NATURE COMMUNICATIONS
(2023)
Article
Biochemical Research Methods
Ashkan Karimi, Kaixiang Wang, Kaleena Basran, William Copp, Nathan W. Luedtke
Summary: A new fluorescent cytosine analog, C-ts, was synthesized and incorporated into hemiprotonated base pairs that form i-motif structures. Unlike previous fluorescent base analogs, C-ts mimics the acid-base properties of cytosine while exhibiting bright and red-shifted fluorescence upon protonation. Ratiometric analysis of C-ts emission wavelengths allows real-time tracking of structural conversions between different DNA structures. Results suggest that hemiprotonated C+:C base pairs can form in partially folded single-stranded DNA in the absence of global i-motif structures.
BIOCONJUGATE CHEMISTRY
(2023)
Article
Microbiology
Inna A. Suvorova, Mikhail S. Gelfand
Summary: Comparative genomics techniques were used to identify binding motifs of IclR-family TFs, reconstruct regulons, and analyze their content. Two main types of IclR-family motifs were described, with possible alternative modes of dimerization, as well as trends in site positioning and protein-DNA contacts. The majority of predicted protein-DNA contacts were similar for both types of motifs and aligned well with available experimental data and general protein-DNA interaction trends.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Xinye Wang, Xiaoran Jing, Yi Deng, Yao Nie, Fei Xu, Yan Xu, Yi-Lei Zhao, John F. Hunt, Gaetano T. Montelione, Thomas Szyperski
Article
Biochemistry & Molecular Biology
Guifang Chen, Li-Chung Ma, Shanshan Wang, Ryan L. Woltz, Emily M. Grasso, Gaetano T. Montelione, Robert M. Krug
NUCLEIC ACIDS RESEARCH
(2020)
Biographical-Item
Chemistry, Physical
Gia G. Maisuradze, Gaetano T. Montelione, Shalom Rackovsky, Jeffrey Skolnick
JOURNAL OF PHYSICAL CHEMISTRY B
(2020)
Article
Biochemistry & Molecular Biology
Sriram Aiyer, G. V. T. Swapna, Li-Chung Ma, Gaohua Liu, Jingzhou Hao, Gordon Chalmers, Brian C. Jacobs, Gaetano T. Montelione, Monica J. Roth
Summary: The ET domain of BRD3 interacts with viral and host proteins through similar beta-sheet formations. N-15 relaxation studies reveal a restricted flexibility in the linker region, affecting its orientation in the protein complexes. The complex of the ET-binding peptide of host NSD3 protein and the BRD3 ET domain shows a different orientation compared to viral protein complexes.
Article
Biochemical Research Methods
Casey A. Cole, Nourhan S. Daigham, Gaohua Liu, Gaetano T. Montelione, Homayoun Valafar
Summary: This study focuses on the development of REDCRAFT, a protein structure modeling program, with a particular emphasis on the Adaptive Decimation (AD) feature. The research demonstrates the successful application of REDCRAFT in determining protein structures ranging from small to large sizes using experimentally collected data.
PLOS COMPUTATIONAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Jitender Mehla, George Liechti, Randy M. Morgenstein, J. Harry Caufield, Ali Hosseinnia, Alla Gagarinova, Sadhna Phanse, Norman Goodacre, Mary Brockett, Neha Sakhawalkar, Mohan Babu, Rong Xiao, Gaetano T. Montelione, Sergey Vorobiev, Tanneke den Blaauwen, John F. Hunt, Peter Uetz
Summary: YhcB, a conserved protein across gamma-proteobacteria with unknown function, plays a crucial role in cell division and affects envelope biogenesis. Based on its interactions with key proteins in divisome and elongasome, it is proposed to be renamed as ZapG for its association with the Z-ring. This study provides insights for future research on the protein family and cell transition from exponential to stationary survival.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Cell Biology
Khushboo Bafna, Kris White, Balasubramanian Harish, Romel Rosales, Theresa A. Ramelot, Thomas B. Acton, Elena Moreno, Thomas Kehrer, Lisa Miorin, Catherine A. Royer, Adolfo Garcia-Sastre, Robert M. Krug, Gaetano T. Montelione
Summary: Some hepatitis C virus protease inhibitor drugs can inhibit SARS-CoV-2 virus replication and enhance the antiviral activity of other drugs, but not all drugs have this effect.
Article
Multidisciplinary Sciences
Nobuyasu Koga, Rie Koga, Gaohua Liu, Javier Castellanos, Gaetano T. Montelione, David Baker
Summary: The study successfully applied the principles of designing ideal proteins with consistent local and non-local interactions to design larger proteins with five- and six-stranded beta-sheets flanked by alpha-helices. Investigation revealed that the global structures of the design models were more strained than the NMR structures. By incorporating explicit consideration of global backbone strain, proteins with the intended unswapped strand arrangements were successfully designed, highlighting the importance of global tertiary interactions in determining protein topology.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Yuanpeng Janet Huang, Ning Zhang, Beate Bersch, Krzysztof Fidelis, Masayori Inouye, Yojiro Ishida, Andriy Kryshtafovych, Naohiro Kobayashi, Yutaka Kuroda, Gaohua Liu, Andy LiWang, G. V. T. Swapna, Nan Wu, Toshio Yamazaki, Gaetano T. Montelione
Summary: NMR studies provide unique information on protein conformations in solution, with CASP14 showing varying prediction results for targets with NMR-based structures. By comparing prediction models and experimental NMR data, new methods were explored for guiding NMR data analysis.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2021)
Article
Biochemistry & Molecular Biology
Daniel R. Colman, Gilles Labesse, Gurla V. T. Swapna, Johanna Stefanakis, Gaetano T. Montelione, Eric S. Boyd, Catherine A. Royer
Summary: Dissimilatory sulfite reductase (DsrAB), an ancient enzyme, plays an important role in linking sulfur and carbon biogeochemical cycles. Through structural and evolutionary analyses, this study provides insights into the conservation of certain structural features in DsrAB and reveals potential allosteric communication pathways between subunits. These findings lay a foundation for future research on the biochemical and structural properties of DsrAB.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2022)
Article
Cell Biology
Yuan Wang, Bochao Liu, Huimei Lu, Jingmei Liu, Peter J. Romanienko, Gaetano T. Montelione, Zhiyuan Shen
Summary: This study identifies a regulatory mechanism by which the cytoplasmic function of KU70 is enabled through methylation by SETD4. Mutations of SETD4 prevent methylation of KU70. The findings also reveal the importance of SETD4 and KU70K570 methylation in the suppression of apoptosis.
Article
Biochemistry & Molecular Biology
Yaohui Li, Rongzhen Zhang, Chi Wang, Farhad Forouhar, Oliver B. Clarke, Sergey Vorobiev, Shikha Singh, Gaetano T. Montelione, Thomas Szyperski, Yan Xu, John F. Hunt
Summary: The evolutionary benefit of oligomeric structures in proteins lacking evidence of intersubunit cooperativity is unclear. In this study, a conserved tetramer interface is shown to maintain the active-site structure in a certain class of proteins, the SDR superfamily. Oligomerization reduces the metabolic cost of enzyme biosynthesis and increases tolerance to destabilizing mutations, enhancing evolutionary fitness.
Article
Biochemistry & Molecular Biology
Roberto Tejero, Yuanpeng Janet Huang, Theresa A. Ramelot, Gaetano T. Montelione
Summary: Recent advances in molecular modeling, particularly AlphaFold, have the potential to revolutionize structural biology, as it provides protein structure models with accuracies similar to or even better than experimental data. This holds promise for guiding the analysis of experimental data and has broader applications in the field.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Gaurav Bhardwaj, Jacob O'Connor, Stephen Rettie, Yen-Hua Huang, Theresa A. Ramelot, Vikram Khipple Mulligan, Gizem Gokce Alpkilic, Jonathan Palmer, Asim K. Bera, Matthew J. Bick, Maddalena Di Piazza, Xinting Li, Parisa Hosseinzadeh, Timothy W. Craven, Roberto Tejero, Anna Lauko, Ryan Choi, Calina Glynn, Linlin Dong, Robert Griffin, Wesley C. van Voorhis, Jose Rodriguez, Lance Stewart, Gaetano T. Montelione, David Craik, David Baker
Summary: This study investigates the design principles for macrocycle membrane permeability and oral bioavailability using computational design and experimental characterization. The results show that membrane permeability can be achieved by engaging all amide (NH) groups in internal hydrogen bonding interactions. Additionally, designs with exposed NH groups can be made membrane permeable through the design of an alternative isoenergetic fully hydrogen-bonded state favored in the lipid membrane. The ability to design membrane-permeable and orally bioavailable peptides with high structural accuracy has significant implications for the development of next-generation macrocycle therapeutics.
Article
Biochemical Research Methods
Keith J. Fraga, Yuanpeng J. Huang, Theresa A. Ramelot, G. V. T. Swapna, Arwin Lashawn Anak Kendary, Ethan Li, Ian Korf, Gaetano T. Montelione
Summary: NMR is a valuable experimental tool for structural biologists to study biomolecules. The progress of machine learning highlights the importance of large, diverse, and reliable datasets in structural biology. By organizing NMR data and using machine learning methods, long-standing problems in NMR data processing and structure determination can be tackled.
JOURNAL OF MAGNETIC RESONANCE
(2022)
