Article
Biology
Ruben Rosas, Rhiannon R. Aguilar, Nina Arslanovic, Anna Seck, Duncan J. Smith, Jessica K. Tyler, Mair E. A. Churchill
Summary: The histone chaperone CAF-1 deposits histone H3/H4 dimers onto newly replicated DNA to form the central core of the nucleosome tetrasome. The KER SAH region of CAF-1 plays a crucial role in ensuring the assembly of tetrasomes by linking functional domains within CAF-1 with structural precision.
Review
Oncology
Ting Wen, Qiao Yi Chen
Summary: This article discusses the translation regulatory mechanisms of histone H3.1 and H3.3 and their roles in tumorigenesis.
FRONTIERS IN ONCOLOGY
(2022)
Review
Cell Biology
Peijun Wang, Wanting Yang, Shuxin Zhao, Buhe Nashun
Summary: This article discusses the important role of the histone chaperone facilitates chromatin transcription (FACT) in the cell cycle, analyzing its structural characteristics and functions. It explores how FACT regulates chromatin reorganization and its potential roles in transcription, replication, DNA repair, and even cell fate determination.
Article
Cell Biology
Chao-Pei Liu, Wenxing Jin, Jie Hu, Mingzhu Wang, Jingjing Chen, Guohong Li, Rui-Ming Xu
Summary: In this study, Liu et al. investigated how sNASP binds H3-H4 in the presence and absence of ASF1, two major histone H3-H4 chaperones found in distinct and common complexes, during chromosomal duplication. They show that, in the presence of ASF1, sNASP principally recognizes a partially unfolded N alpha region of histone H3, and in the absence of ASF1, an additional sNASP binding site becomes available in the core domain of the H3-H4 complex, providing new mechanistic insights into coordinated histone binding and transfer by histone chaperones.
GENES & DEVELOPMENT
(2021)
Article
Biochemistry & Molecular Biology
Sara Garcia-Alonso, Pablo Mesa, Laura de la Puente Ovejero, Gonzalo Aizpurua, Carmen G. Lechuga, Eduardo Zarzuela, Clara M. Santiveri, Manuel Sanclemente, Javier Munoz, Monica Musteanu, Ramon Campos-Olivas, Jorge Martinez-Torrecuadrada, Mariano Barbacid, Guillermo Montoya
Summary: This study describes the structure of the RAF1 protein in complex with HSP90 and CDC37. The research reveals that CDC37 can differentiate between different members of the RAF family. Additionally, the study shows that folded RAF1 assembles with 14-3-3 dimers, and disrupting the interaction between CDC37 and RAF1 may have potential therapeutic implications.
Article
Biology
Alonso Javier Pardal, Andrew James Bowman
Summary: This study identified importin-5 as the major importin associated with cytoplasmic H3, which transfers its monomeric cargo to nuclear sNASP. Additionally, monomeric H4 interacts specifically with HAT1 and RBBP7. It was found that Imp5 and sNASP compete for binding H3, suggesting a direct interaction site competition requiring GTP-bound Ran for histone transfer.
Article
Biochemistry & Molecular Biology
Julian Broche, Goran Kungulovski, Pavel Bashtrykov, Philipp Rathert, Albert Jeltsch
Summary: This study revealed that DNA methylation introduced in CGIs can significantly decrease gene expression, and is associated with a global decrease in H3K4me3 and H3K27ac, while being stable at some CGIs. The results highlight the importance of genome-wide molecular processes that protect CGIs against DNA methylation.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Huiqi Yin, Zhenlong Kang, Yingwen Zhang, Yingyun Gong, Mengrou Liu, Yanfeng Xue, Wenxiu He, Yanfeng Wang, Shuya Zhang, Qiushi Xu, Kaiqiang Fu, Bangjin Zheng, Jie Xie, Jinwen Zhang, Yuanyuan Wang, Mingyan Lin, Yihan Zhang, Hua Feng, Changpeng Xin, Yichun Guan, Chaoyang Huang, Xuejiang Guo, P. Jeremy Wang, Joseph A. Baur, Ke Zheng, Zheng Sun, Lan Ye
Summary: The study identifies HDAC3 as a key regulator in spermatogenesis, where it represses meiotic/spermatogonial genes and activates postmeiotic haploid gene programs during the meiotic exit. Unexpectedly, abolishing HDAC3 catalytic activity does not affect fertility, demonstrating that HDAC3 enzyme activity is not required for spermatogenesis. Motif analysis of the HDAC3 cistrome in the testes identified SOX30 as a key regulator in the transcriptional program during the meiotic-to-postmeiotic transition in spermatogenesis.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Agriculture, Multidisciplinary
Manli Yang, Jingyu Wu, Qingrong Huang, Yan Jia
Summary: The study found a novel mechanism for the cleavage of the peptide bond between the intramolecular chaperone and the subtilisin domain in a new protease member, nattokinase (NK), which was different from the classical theory. The catalytic triad of NK did not play a consistent role in the cleavage, suggesting that subtilisin family members have evolved different mechanisms to efficiently acquire their own active subtilisin.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2021)
Article
Cell Biology
Eutteum Jeong, Jose A. Martina, Pablo S. Contreras, Juhyung Lee, Rosa Puertollano
Summary: TFEB and TFE3 interact with the FACT complex, regulating the transcription of stress-induced genes. FACT plays a crucial role in regulating cellular homeostasis.
Article
Biology
David C. Klein, Santana M. Lardo, Kurtis N. McCannell, Sarah J. Hainer
Summary: The FACT complex maintains cellular pluripotency by regulating nucleosome positioning and transcription activity. FACT interacts with genes such as OCT4, SOX2, and NANOG, binding to both promoter and enhancer elements, and regulates their transcription and expression, thereby influencing cell fate decisions.
Article
Cell Biology
Ye Yue, Wen-Si Yang, Lin Zhang, Chao-Pei Liu, Rui-Ming Xu
Summary: The study reveals the interaction between H3, H4, Hat1, and Hat2 in the Hat1-Hat2 acetyltransferase complex bound to Asf1-H3-H4. The findings expand our knowledge of histone-protein interaction and suggest a potential role of Hat2/RbAp46/48 in histone transfer.
GENES & DEVELOPMENT
(2022)
Article
Biochemistry & Molecular Biology
Nazmul Haque, Alexander Will, Atlanta G. Cook, J. Robert Hogg
Summary: Proteins with DZF modules have various important roles in gene expression, and they form heterodimerization surfaces between DZF protein pairs. ILF2, ILF3, and ZFR are three widely expressed DZF proteins in mammalian tissues, and they form mutually exclusive heterodimers. ZFR binds to intronic regions to regulate alternative splicing and preferentially binds dsRNA.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Multidisciplinary Sciences
Andreas Herchenroether, Stefanie Gossen, Tobias Friedrich, Alexander Reim, Nadine Daus, Felix Diegmueller, Joerg Leers, Hakimeh Moghaddas Sani, Sarah Gerstner, Leah Schwarz, Inga Stellmacher, Laura Victoria Szymkowiak, Andrea Nist, Thorsten Stiewe, Tilman Borggrefe, Matthias Mann, Joel P. Mackay, Marek Bartkuhn, Annette Borchers, Jie Lan, Sandra B. Hake
Summary: In this study, the authors identified PWWP2A as a direct interactor of histone variant H2A.Z, involved in mitosis and craniofacial development. They also found that HMG20A, which associates with H2A.Z and PWWP2A, is part of chromatin-modifying complexes and localizes to specific genomic regions. Depletion of HMG20A leads to severe developmental defects, including impaired neural crest cell migration and cartilage formation.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Changying Guo, Karla F. Meza-Sosa, David Valle-Garcia, Guomeng Zhao, Kun Gao, Liting Yu, Hongying Zhang, Yeqing Chen, Liang Sun, Shira Rockowitz, Shouyu Wang, Sheng Jiang, Judy Lieberman
Summary: SET is a multifunctional histone-binding oncoprotein that enhances estrogen-dependent transcription. It binds to estrogen receptor alpha (ER alpha) and is recruited to ER alpha-bound enhancers and promoters at estrogen response elements (EREs). SET acts as a histone H2 chaperone, promotes H2A.Z incorporation, and modulates histone methylation at EREs. It also affects enhancer-promoter looping and recruitment of condensin complexes, crucial for E2-induced gene expression and transcriptional activation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Courtney N. Niland, Agnidipta Ghosh, Sean M. Cahill, Vern L. Schramm
Summary: MAT2A catalyzes the formation of AdoMet through a sequential mechanism, with slow hydrolysis of both ATP and triphosphate. The protein structure of MAT2A is highly stabilized against denaturation by the presence of PNPNP.
Article
Operations Research & Management Science
Jose F. S. Bravo-Ferreira, David Cowburn, Yuehaw Khoo, Amit Singer
Summary: Nuclear Magnetic Resonance (NMR) Spectroscopy is a key technique for protein structure determination, with a challenge being the assignment of resonance frequencies to atoms. The introduction of LIAN, a novel linear programming formulation, has led to state-of-the-art results in simulated and experimental datasets.
JOURNAL OF GLOBAL OPTIMIZATION
(2022)
Article
Otorhinolaryngology
Jerome M. Karp, Kenneth S. Hu, Michael Persky, Mark Persky, Adam Jacobson, Theresa Tran, Zujun Li, Babak Givi, Moses M. Tam
Summary: Sinonasal cancers often present as advanced diseases, and national guidelines recommend systemic therapy and radiotherapy for managing T4b tumors. Recent studies suggest that adding surgical resection may improve local control and survival rates. Analysis of the National Cancer Database showed that incorporating surgery in the treatment of T4b sinonasal squamous cell carcinoma was associated with promising survival outcomes.
OTOLARYNGOLOGY-HEAD AND NECK SURGERY
(2022)
Article
Biochemistry & Molecular Biology
Irimpan I. Mathews, Naoki Horikoshi, Tsutomu Matsui, Manat Kaur, Soichi Wakatsuki, Daria Mochly-Rosen, Adriana Ann Garcia
Summary: This study identified a small molecule that activates G6PD variants by stabilizing the allosteric NADP(+) and dimer complex, suggesting potential therapeutic strategies for G6PD deficiency. The connection between allosteric NADP+ binding, oligomerization, and pathogenicity was elucidated, and stabilizing the dimer and tetramer was found to improve protein stability and activity. These findings provide a foundation for future drug discovery efforts.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Microbiology
Ryan J. Malonis, George Georgiev, Denise Haslwanter, Laura A. VanBlargan, Georgia Fallon, Olivia Vergnolle, Sean M. Cahill, Richard Harris, David Cowburn, Kartik Chandran, Michael S. Diamond, Jonathan R. Lai
Summary: By creating a subunit-based nanoparticle immunogen, we were able to induce the production of neutralizing and protective antibodies against POWV infection in mice. Our study provides insights into the molecular determinants of antibody-mediated neutralization and protection against TBFVs.
Article
Chemistry, Multidisciplinary
Giridhar Sekar, Adam J. Stevens, Anahita Z. Mostafavi, Pulikallu Sashi, Tom W. Muir, David Cowburn
Summary: Split intein-mediated protein trans-splicing (PTS) is a widely used method in chemical biology and biotechnology for traceless and specific protein ligation. The efficiency of PTS can be limited by external residues flanking the intein. In this study, a recently developed atypically split intein (Cat) was further modified to enhance its PTS activity in the presence of unfavorable N-extein residues. The mechanism behind the enhanced activity was explored using nuclear magnetic resonance spectroscopy and molecular dynamics simulations, highlighting the contribution of a conserved histidine residue. This enhanced extein tolerance of Cat* expands the applicability of atypically split inteins and reveals common principles of extein dependence.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Biochemical Research Methods
Jill Trewhella, Patrice Vachette, Jan Bierma, Clement Blanchet, Emre Brookes, Srinivas Chakravarthy, Leonie Chatzimagas, Thomas E. Cleveland, Nathan Cowieson, Ben Crossett, Anthony P. Duff, Daniel Franke, Frank Gabel, Richard E. Gillilan, Melissa Graewert, Alexander Grishaev, J. Mitchell Guss, Michal Hammel, Jesse Hopkins, Qingqui Huang, Jochen S. Hub, Greg L. Hura, Thomas C. Irving, Cy Michael Jeffries, Cheol Jeong, Nigel Kirby, Susan Krueger, Anne Martel, Tsutomu Matsui, Na Li, Javier Perezt, Lionel Porcar, Thierry Prange, Ivan Rajkovic, Mattia Rocco, Daniel J. Rosenberg, Timothy M. Ryan, Soenke Seifert, Hiroshi Sekiguchi, Dmitri Svergun, Susana Teixeira, Aurelien Thureaut, Thomas M. Weiss, Andrew E. Whitten, Kathleen Wood, Xiaobing Zuo
Summary: By collecting SAXS and SANS measurements, consensus scattering profiles for proteins were obtained, which were consistent with theoretical predictions. Optimization of sample purification methods and measurement conditions can improve the quality and precision of the data.
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY
(2022)
Editorial Material
Oncology
Jerome M. Karp
PRACTICAL RADIATION ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Yacoba V. T. Minnow, Kajitha Suthagar, Keith Clinch, Rodrigo G. Ducati, Agnidipta Ghosh, Joshua N. Buckler, Rajesh K. Harijan, Sean M. Cahill, Peter C. Tyler, Vern L. Schramm
Summary: Plasmodium falciparum hypoxanthine-guanine-xanthine phosphoribosyltransferase (PfHGXPRT) is an essential enzyme for the salvage pathway of hypoxanthine into parasite purine nucleotides. In this study, transition state analogue inhibitors of PfHGXPRT were characterized using kinetic analysis, thermodynamic parameters, and X-ray crystal structures. Compound 1, which is an acyclic ribocation phosphonate mimic linked to 9-deazaguanine, showed a kinetic Ki of 0.5 nM. Isothermal titration calorimetry experiments revealed enthalpically driven binding of compound 1 to PfHGXPRT with negative cooperativity. Crystal structures of the inhibitor bound to the enzyme provided insights into the hydrogen bond and ionic contacts involved in the binding process. The dynamics of ribosyl transfer from 5-phospho-alpha-D-ribosyl 1-pyrophosphate (PRPP) to hypoxanthine were investigated using 18O isotope exchange, which showed that rotational constraints and short transition state lifetimes prevented positional isotope exchange. The thermodynamic analysis of the transition state analogue and magnesium pyrophosphate binding indicated random and cooperative binding to PfHGXPRT, suggesting a different mechanism from the previously reported substrate kinetics.
ACS CHEMICAL BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
David Cowburn, Michael Rout
Summary: Nuclear pore complexes (NPCs) play a crucial role in material exchange between the nucleus and cytoplasm, with a specific focus on nucleic acids and proteins. While the static structure of NPCs has been well defined, the functional roles of certain dynamic components, such as phenylalanyl-glycyl (FG) repeat rich nucleoporins, remain unclear. However, advancements in technical approaches and modeling methods may soon provide a more accurate and detailed understanding of NPC transport, potentially at the atomic level. Such progress would be invaluable in comprehending the impact of malfunctioning NPCs in various diseases.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2023)
Article
Biophysics
Bright Shi, Tsutomu Matsui, Shuo Qian, Thomas M. Weiss, Iain D. Nicholl, David J. E. Callaway, Zimei Bu
Summary: The cell-cell adhesion cadherin-catenin complexes recruit vinculin to the adherens junction (AJ), but the specific influence of vinculin on AJ structure and function remains unclear. This study identifies two patches of salt bridges that lock vinculin in an autoinhibited conformation and reconstitutes the vinculin activation mimetics bound to the cadherin-catenin complex. The dynamic cadherin-catenin-vinculin complex employs vinculin as the primary F-actin binding mode to strengthen AJ-cytoskeleton interactions.
BIOPHYSICAL JOURNAL
(2023)
Meeting Abstract
Chemistry, Multidisciplinary
Thomas Weiss, Tsutomu Matsui, Ivan Rajkovic, Ping Liu
ACTA CRYSTALLOGRAPHICA A-FOUNDATION AND ADVANCES
(2022)
Article
Biochemistry & Molecular Biology
George Georgiev, Ryan J. Malonis, Ariel S. Wirchnianski, Alex W. Wessel, Helen S. Jung, Sean M. Cahill, Elisabeth K. Nyakatura, Olivia Vergnolle, Kimberly A. Dowd, David Cowburn, Theodore C. Pierson, Michael S. Diamond, Jonathan R. Lai
Summary: Researchers have developed a recombinant ZIKV immunogen using protein engineering techniques, which can elicit a protective immune response with reduced potential for producing enhancing antibodies.
CELL CHEMICAL BIOLOGY
(2022)