Article
Biochemistry & Molecular Biology
Weibin Gong, Qihui Liang, Yufeng Tong, Sarah Perrett, Yingang Feng
Summary: RBBP1 is involved in gene regulation, epigenetic regulation, and disease processes. The ARID domain in RBBP1 plays a key role in DNA binding and gene suppression, with unexpected involvement of the disordered acidic loop L12.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Immunology
Yi Zhong, Sarah K. Walker, Yuri Pritykin, Christina S. Leslie, Alexander Y. Rudensky, Joris van der Veeken
Summary: Zhong et al. studied the transcriptional regulation of T cell gene expression upon viral challenge using B6/Cast F1 hybrid mice. They found that members of Ets, Runx, and TCF/Lef transcription factor families play key roles in maintaining or increasing chromatin accessibility during T cell activation. Some highly induced immune response genes exhibit a noncanonical TF recruitment pattern.
Article
Biotechnology & Applied Microbiology
Xiaoxue Ma, Qianhan Lin, Gongting Cui, Jing Zhao, Xuan Wei, Rui Li, Hongluan Mao, Yanhui Ma, Peishu Liu, Yingxin Pang
Summary: In endometrial carcinoma, the expression level of GABPA is closely related to prognosis, with low levels indicating poorer overall survival and disease-free survival. GABPA may serve as an independent predictor of clinical prognosis and a potential target gene for EC therapy.
Article
Hematology
Rina Nishii, Rebekah Baskin-Doerfler, Wentao Yang, Ninad Oak, Xujie Zhao, Wenjian Yang, Keito Hoshitsuki, Mackenzie Bloom, Katherine Verbist, Melissa Burns, Zhenhua Li, Ting-Nien Lin, Maoxiang Qian, Takaya Moriyama, Julie M. Gastier-Foster, Karen R. Rabin, Elizabeth Raetz, Charles Mullighan, Ching-Hon Pui, Allen Eng-Juh Yeoh, Jinghui Zhang, Monika L. Metzger, Jeffery M. Klco, Stephen P. Hunger, Scott Newman, Gang Wu, Mignon L. Loh, Kim E. Nichols, Jun J. Yang
Summary: Research shows that germline ETV6 variants can affect susceptibility to acute lymphoblastic leukemia and lead to a novel leukemia predisposition syndrome. Variants in ETV6 impact DNA binding, transcriptional repressor activity, and nuclear localization, influencing the genomic landscape, karyotype, and gene expression patterns of leukemia cells.
Article
Chemistry, Physical
Souvik Dey, Huan-Xiang Zhou
Summary: This study used molecular dynamics simulations to investigate the regulation of the IDP N-WASP, finding that intramolecular interactions keep N-WASP in an autoinhibited state and PIP2 binding can activate it by freeing the acidic motif, which interacts with Arp2/3 to initiate actin polymerization. Competition exists between PIP2 and the acidic motif for binding to the basic region. Even at a 30% PIP2 level in the membrane, the acidic motif only contacts the basic region in 8.5% of the population.
JOURNAL OF CHEMICAL PHYSICS
(2023)
Article
Multidisciplinary Sciences
Yanli Dong, Hang Li, Alina Ilie, Yiwei Gao, Annie Boucher, Xuejun Cai Zhang, John Orlowski, Yan Zhao
Summary: Sodium-proton exchanger 3 (NHE3/SLC9A3) plays an important role in regulating salt and fluid absorption as well as pH homeostasis. Calcineurin B homologous protein 1 (CHP1) acts as an auxiliary regulatory factor for NHE3, promoting its maturation and plasmalemmal expression. Cryo-electron microscopy structure analysis revealed that a cytosolic helix-loop-helix motif in NHE3 inhibits substrate transport, and the binding of phosphatidylinositol molecules stabilizes the complex and enhances its transport activity.
Article
Biochemistry & Molecular Biology
Thor van Heesch, Peter G. Bolhuis, Jocelyne Vreede
Summary: Sequence-specific protein-DNA interactions play a crucial role in DNA organization, gene regulation, and DNA replication. This study presents a molecular simulation approach that allows for the quantification of sequence specificity in protein-DNA complexes. The approach, based on molecular dynamics simulations, provides insights into recognition mechanisms and offers predictions of nucleotide-specific binding affinity. The results are in agreement with experimental data and can be applied to a wide range of protein-DNA complexes.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Chemistry, Physical
Tam D Vo, Amelia L. Schneider, W. David Wilson, Gregory M. K. Poon
Summary: Electrostatic interactions between protein and DNA involve neutralization of the DNA backbone and exchanges by charged residues. While much attention has been given to interfacial ion pairs, the role of extra-interfacial ionic interactions in DNA sequence selectivity remains unclear. By comparing the salt-dependent binding of two ETS homologs, Elk1 and ETV6, with differing ionic compositions, it was found that variations in primary structure ionic residues can lead to differentiated specificity mechanisms in a highly conserved DNA-binding motif.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2021)
Article
Biology
Keijun Kakihara, Kengo Asamizu, Kei Moritsugu, Masahide Kubo, Tetsuya Kitaguchi, Akinori Endo, Akinori Kidera, Mitsunori Ikeguchi, Akira Kato, Masayuki Komada, Toshiaki Fukushima
Summary: This study identified amino acids 645-684 of USP8 as an autoinhibitory region and suggested that the release of USP8 autoinhibition may underlie Cushing's disease. The findings also indicate that 14-3-3 inhibits USP8 activity partly by enhancing the interaction between the WW-like and USP domains.
COMMUNICATIONS BIOLOGY
(2021)
Review
Genetics & Heredity
Brian Thompson, Emily A. Davidson, Wei Liu, Daniel W. Nebert, Elspeth A. Bruford, Hongyu Zhao, Emmanouil T. Dermitzakis, David C. Thompson, Vasilis Vasiliou
Summary: PAX genes encode highly conserved transcription factors that regulate cell differentiation and organ development. Different structural domains in PAX proteins categorize them into four groups, playing crucial roles in various human diseases.
Article
Chemistry, Analytical
LianLian Xu, Weihua Zhao, Jiamei Pu, Suqin Wang, Shiwen Liu, Hongbo Li, Ruqin Yu
Summary: In this study, a biosensor based on Lambda exonuclease and HCR enzyme-free amplification system was designed to detect Pax-5a gene with high sensitivity. The biosensor showed advantages of simple operation, high sensitivity, and good selectivity, and has potential applications in the early diagnosis of leukemia and biosensor design.
ANALYTICAL METHODS
(2022)
Article
Cell Biology
Desiree M. Baron, Adam R. Fenton, Sara Saez-Atienzar, Anthony Giampetruzzi, Aparna Sreeram, Shankaracharya, Pamela J. Keagle, Victoria R. Doocy, Nathan J. Smith, Eric W. Danielson, Megan Andresano, Mary C. McCormack, Jaqueline Garcia, Valerie Bercier, Ludo Van den Bosch, Jonathan R. Brent, Claudia Fallini, Bryan J. Traynor, Erika L. F. Holzbaur, John E. Landers
Summary: Understanding the pathogenic mechanisms of disease mutations is crucial for advancing treatments. This study found that ALS-associated mutations in the gene encoding microtubule motor KIF5A result in the production of a protein with an abnormal C-terminal sequence, leading to motor activity dysregulation and decreased neuronal survival. These findings shed light on the disruptive effects of pathogenic mutations on intracellular trafficking and neuronal homeostasis.
Article
Multidisciplinary Sciences
Irene Cosi, Annalisa Moccia, Chiara Pescucci, Uday Munagala, Salvatore Di Giorgio, Irene Sineo, Silvestro G. G. Conticello, Rosario Notaro, Maria De Angioletti
Summary: ETV4, an overexpressed ETS protein in prostate cancer, promotes migration, invasion, and proliferation in prostate cells. This study identifies previously unknown ETV4 alternatively spliced transcripts in human prostate cell lines and confirms their presence in prostate tumors. The abundance of these transcripts may reflect tumor deranged splicing machinery and their potential interactions with canonical variants may contribute to the biology and clinics of prostate cancer. Further investigations are needed to understand the biological role of these ETV4 transcripts and their isoforms.
SCIENTIFIC REPORTS
(2023)
Article
Hematology
Emily R. Legan, Yi Liu, Nicholas A. Arce, Ernest T. Parker, Pete Lollar, X. Frank Zhang, Renhao Li
Summary: Type 2B von Willebrand disease is an inherited bleeding disorder caused by point mutations in the von Willebrand factor A1 domain and autoinhibitory module, leading to enhanced binding to GPIb alpha. The severity of bleeding complications and platelet levels in patients varies depending on the underlying mutation. This study examines the thermodynamic stability, conformational dynamics, and biomechanical regulation of these mutations to understand the heterogeneity among them.
Article
Biochemistry & Molecular Biology
Bryan VanSchouwen, Jinfeng Huang, Ubaidullah Baryar, Giuseppe Melacini, Jung Ah Byun
Summary: This study reveals significant differences in the allosteric networks of the essential CBDs between the Plasmodium falciparum cGMP-dependent protein kinase (pfPKG) and human cGMP-dependent protein kinase (hPKG). The findings provide crucial insights into potential drug targets for selective inhibition of pfPKG versus hPKG, which could help reduce side effects in malaria treatments.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Allergy
Yapeng Li, Bing Liu, Laura Harmacek, Zijie Long, Jinyi Liang, Kara Lukin, Sonia M. Leach, Brian O'Connor, Anthony N. Gerber, James Hagman, Axel Roers, Fred D. Finkelman, Hua Huang
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2018)
Article
Oncology
S. J. Welsh, M. L. Churchman, M. Togni, C. G. Mullighan, J. Hagman
Article
Hematology
Giovanny Hernandez, Taylor S. Mills, Jennifer L. Rabe, James S. Chavez, Susan Kuldanek, Gregory Kirkpatrick, Leila Noetzli, Widian K. Jubair, Michelle Zanche, Jason R. Myers, Brett M. Stevens, Courtney J. Fleenor, Biniam Adane, Charles A. Dinarello, John Ashton, Craig T. Jordan, Jorge Di Paola, James R. Hagman, V. Michael Holers, Kristine A. Kuhn, Eric M. Pietras
Article
Multidisciplinary Sciences
Tessa Arends, Carissa Dege, Alexandra Bortnick, Thomas Danhorn, Jennifer R. Knapp, Haiqun Jia, Laura Harmacek, Courtney J. Fleenor, Desiree Straign, Kendra Walton, Sonia M. Leach, Ann J. Feeney, Cornelis Murre, Brian P. O'Connor, James R. Hagman
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2019)
Article
Biochemistry & Molecular Biology
Lauren T. Que, Marie E. Morrow, Cynthia Wolberger
Article
Biology
Evan J. Worden, Xiangbin Zhang, Cynthia Wolberger
Article
Multidisciplinary Sciences
Yapeng Li, Junfeng Gao, Mohammad Kamran, Laura Harmacek, Thomas Danhorn, Sonia M. Leach, Brian P. O'Connor, James R. Hagman, Hua Huang
Summary: The study demonstrates that GATA2 promotes chromatin accessibility at the super-enhancers of mast cell identity genes and primes both typical and super-enhancers at genes that respond to antigenic stimulation.
NATURE COMMUNICATIONS
(2021)
Article
Hematology
Rajesh Somasundaram, Christina T. Jensen, Johanna Tingvall-Gustafsson, Josefine Ahsberg, Kazuki Okuyama, Mahadesh Prasad, James R. Hagman, Xun Wang, Shamit Soneji, Tobias Strid, Jonas Ungerback, Mikael Sigvardsson
Summary: The study reveals that EBF1 directly regulates the Myc gene and EBF1 and PAX5 have opposing roles in regulating Myc levels. Experimental results demonstrate that EBF1 and PAX5 interact with each other in pro-B cell expansion and play important roles in regulating the MYC gene.
Review
Biochemistry & Molecular Biology
Cynthia Wolberger
Summary: Over the past four decades, significant progress has been made in our understanding of the structural basis of gene regulation, thanks to technological advances in protein expression, nucleic acid synthesis, and structural biology. This review focuses on insights gained from structural studies of protein-DNA complexes and the role the Protein Data Bank has played in driving this research. From X-ray crystal structures to recent cryo-EM structures, the highlights of the field are covered, detailing the study of transcription factors binding to nucleosomal DNA.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Review
Immunology
James R. Hagman, Tessa Arends, Curtis Laborda, Jennifer R. Knapp, Laura Harmacek, Brian P. O'Connor
Summary: CHD4 is essential for the development, proliferation, and survival of B cells, as well as for promoting the recombination of the Ig heavy chain and regulating chromatin accessibility, leading to antibody production and mediating humoral immune responses.
IMMUNOLOGICAL REVIEWS
(2022)
Article
Multidisciplinary Sciences
Sanim Rahman, Niklas A. Hoffmann, Evan J. Worden, Marissa L. Smith, Kevin E. W. Namitz, Bruce A. Knutson, Michael S. Cosgrove, Cynthia Wolberger
Summary: This study determines the structure of the MLL1-WRAD complex bound to ubiquitinated nucleosomes using an integrated approach. The structure reveals the conformation of Ash2L's intrinsically disordered region, SPRY insertion region, Sdc1-DPY30 interacting region, and DPY30 dimer. The study also uncovers different states of MLL1-WRAD during its assembly. The docking of subunits in the complex differs when bound to ubiquitinated nucleosomes, indicating the role of ubiquitin in promoting the formation of the active complex.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
James K. Fields, Chad W. Hicks, Cynthia Wolberger
Summary: Post-translational modification of histones, including methylation and monoubiquitination, plays a crucial role in transcription regulation. Methylation of H3K4 and H3K79 activates transcription, while methylation of H3K27 represses transcription. These modifications are dependent on prior monoubiquitination of specific histone residues, leading to a phenomenon called histone crosstalk. Recent studies have provided new insights into the mechanisms of how these modifications regulate the activity of various histone-modifying enzymes.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Fan Zhao, Chad W. Hicks, Cynthia Wolberger
Summary: This study reveals the mechanism by which the E3 ligase Bre1 directs monoubiquitination of histone H2B at K123 by the E2 ubiquitin-conjugating enzyme Rad6, and compares the roles of other dimeric E3 ligases, suggesting a mechanism of tuning histone residue specificity.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Michael Morgan, Tatsuya Ikenoue, Hiroaki Suga, Cynthia Wolberger
Summary: The Spt-Ada-Gcn5 acetyltransferase (SAGA) transcriptional coactivator contains a subcomplex called the deubiquitinating enzyme (DUB) module that can remove ubiquitin from histone H2B-K120. The human DUB module includes the catalytic subunit ubiquitin-specific protease 22 (USP22), which is overexpressed in certain cancers resistant to existing therapies. By screening a large library of cyclic peptides, potent inhibitors of USP22 were identified. The top hit showed high specificity for USP22 and was able to enter human cells and inhibit H2B deubiquitination.
CELL CHEMICAL BIOLOGY
(2022)
Article
Biology
Melesse Nune, Michael T. Morgan, Zaily Connell, Laura McCullough, Muhammad Jbara, Hao Sun, Ashraf Brik, Tim Formosa, Cynthia Wolberger
Article
Biochemistry & Molecular Biology
Ankita Chadda, Alexander G. Kozlov, Binh Nguyen, Timothy M. Lohman, Eric A. Galburt
Summary: In this study, it was found that the DNA damage response in Mycobacterium tuberculosis differs from well-studied model bacteria. The DNA repair helicase UvrD1 in Mtb is activated through a redox-dependent process and is closely associated with the homo-dimeric Ku protein. Additionally, Ku protein is shown to stimulate the helicase activity of UvrD1.
JOURNAL OF MOLECULAR BIOLOGY
(2024)