Review
Biochemistry & Molecular Biology
Jennifer Y. Cui, George P. Lisi
Summary: Cytokines play a key role in cellular communication and biological regulation. Their timing, quantity, and localization are crucial in producing specific biological outcomes. Through molecular observation, insights gained may complement a system-level understanding of cytokine biology, explaining the diversity of downstream signaling events and informing therapeutic and experimental development.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Review
Endocrinology & Metabolism
Brice Beinsteiner, Isabelle M. L. Billas, Dino Moras
Summary: Hepatocyte Nuclear Factor 4 (HNF4) is a transcription factor that plays a crucial role in regulating liver-specific gene expression. Dysregulation of HNF4 is associated with human diseases like type I diabetes and hemophilia. This review focuses on the structures of HNF4 and its impact on the receptor's structure-function relationship.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Joseph N. Fakhoury, Yifan Zhang, Katherine A. Edmonds, Mauro Bringas, Justin L. Luebke, Giovanni Gonzalez-Gutierrez, Daiana A. Capdevila, David P. Giedroc
Summary: CstR is a protein that senses persulfides and regulates bacterial response to hydrogen sulfide and other oxidized reactive sulfur species. Research suggests that the specificity of CstRs to different oxidants is determined by their sequence, structural, and kinetic features.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Multidisciplinary Sciences
Jelle Jacobs, Michaela Pagani, Christoph Wenzl, Alexander Stark
Summary: This study finds that in Drosophila, most enhancers are repressed by only a subset of co-repressors (CoRs), and enhancers classified by CoR sensitivity show distinct chromatin features, function, TF motifs, and binding. Different TF motifs render enhancers more resistant or sensitive to specific CoRs, resulting in the additional layer of regulatory specificity for differential regulation at close genomic distances and indicative of distinct mechanisms of transcriptional repression.
Article
Biochemistry & Molecular Biology
Amar Pratap Singh, Rakesh Kumar, Dinesh Gupta
Summary: Human PRMT4, also known as CARM1, is a type I arginine methyltransferase protein. Structural studies reveal the importance of the N-terminal region, Rossman fold, and dimerization arm in PRMT4 activity. Further elucidation is needed on the communication pathways in PRMT4. Molecular dynamics simulations and network analysis show differences in monomeric and dimeric forms of hPRMT4, as well as the existence of communication networks and an allosteric pathway. These findings provide insights into conformational changes, dimerization mechanism, SAM binding, and inhibitor design for hPRMT4.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Biotechnology & Applied Microbiology
Thomas E. Speltz, Zeyu Qiao, Colin S. Swenson, Xianghang Shangguan, John S. Coukos, Christopher W. Lee, Deborah M. Thomas, Jesse Santana, Sean W. Fanning, Geoffrey L. Greene, Raymond E. Moellering
Summary: Synthetic transcriptional repressors (STRs) derived from the bHLH domain of MAX have been developed using a chemical strategy. These STRs can bind to MYC/MAX consensus E-box motif with high affinity, show specificity comparable to or better than full-length TFs, compete with MYC/MAX protein for DNA binding, and inhibit MYC-dependent expression and cell proliferation. Co-crystallization and structure determination confirm that STRs retain the DNA recognition capability similar to full-length bHLH TFs. Furthermore, STRs derived from alternative bHLH-TFs can also be designed, enabling the development of highly specific mimetics targeting different gene regulatory elements.
NATURE BIOTECHNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Xiaolong Li, Bo Li, Jun Li, Mingyuan Yang, Yushu Bai, Kai Chen, Ziqiang Chen, Ningfang Mao
Summary: Calcium (Ca2+) signaling plays a crucial role in cellular functions, and the binding of Ca2+/CaM to DAPK1 regulates intracellular signaling pathways. This study used molecular dynamics simulations to reveal the importance of Ca2+ in the conformational dynamics of DAPK1-CaM interactions. The results showed that removal of Ca2+ weakened the interactions between DAPK1 and CaM and caused significant conformational changes at the DAPK1-CaM interface.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Sunil Kumar Yadav, Ankita Magotra, Srayan Ghosh, Aiswarya Krishnan, Amrita Pradhan, Rahul Kumar, Joyati Das, Mamta Sharma, Gopaljee Jha
Summary: Bacteria utilize type VI secretion system (T6SS) to deliver antibacterial toxins to target co-habiting bacteria. Burkholderia gladioli strain NGJ1 deploys certain T6SS effectors (TseTBg), having both DNase and RNase activities to kill target bacteria. The associated immunity (TsiTBg) proteins harbor non-canonical helix-turn-helix motifs and demonstrate transcriptional repression activity, similar to the antitoxins of type II toxin-antitoxin (TA) systems.
Article
Biochemistry & Molecular Biology
Gaurika Garg, Christian Dienemann, Lucas Farnung, Juliane Schwarz, Andreas Linden, Henning Urlaub, Patrick Cramer
Summary: We provide mechanistic insights into the three major steps of human co-transcriptional pre-mRNA capping based on six different cryo-EM structures. The human mRNA capping enzyme, RNGTT, first docks to the Pol II stalk to position its triphosphatase domain near the RNA exit site. The capping enzyme then moves onto the Pol II surface, and its guanylyltransferase receives the pre-mRNA 5'-diphosphate end.
Article
Multidisciplinary Sciences
Inokentijs Josts, Katharina Veith, Vincent Normant, Isabelle J. Schalk, Henning Tidow
Summary: The study reported the crystal structure of the inner membrane protein FoxB, revealing its mechanism in Fe-siderophore uptake. Through in vitro assays and in vivo studies, the results establish FoxB as an inner membrane reductase involved in releasing iron from ferrioxamine during Fesiderophore uptake.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Biochemistry & Molecular Biology
David E. Heppner
Summary: The activity of SFKs kinases is regulated by protein phosphorylation, and the oxidation state of their redox-active cysteine residues is influenced by the local structural environment. Conserved and non-conserved cysteine residues exhibit differences in oxidation activity and structural environments.
Review
Biochemistry & Molecular Biology
Romualdo Troisi, Nicole Balasco, Ida Autiero, Luigi Vitagliano, Filomena Sica
Summary: In this paper, the structural aspects of protein-aptamer recognition process were reviewed by surveying the content of the Protein Data Bank. The study identified a significant increase in the number of determined structures of protein-aptamer complexes in the last two years. The complex architectures and the molecular mechanism of the binding process were also analyzed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemical Research Methods
Marketa Soltysova, Irena Sieglova, Milan Fabry, Jiri Brynda, Jana Skerlova, Pavlina Rezacova
Summary: The SorC/DeoR family is a large family of bacterial transcription regulators involved in carbohydrate metabolism and quorum sensing. Structural studies of two members from Bacillus subtilis revealed the structural basis of DNA recognition and proposed a common mode of DNA recognition likely shared by other family members.
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Miaomiao Shen, Wei Huang, Fangjie Qiu, Hengyao Niu, Song Xiang
Summary: This review provides insights into the multiple activities and coordination mechanisms of the budding yeast protein Rad5 and its orthologs, highlighting their critical roles in the cellular response to DNA replication stresses.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Emery T. Usher, Scott A. Showalter
Summary: PDX1 is a central regulator of insulin transcription in pancreatic beta cells, and its function is regulated by cellular cues. However, the molecular mechanisms of PDX1 in glucose response remain elusive. This review summarizes existing studies on PDX1 and provides a comprehensive resource for future research on transcriptional control.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Yifan Zhang, Sambuddha Sen, David P. Giedroc
Article
Biochemistry & Molecular Biology
Abhinaba Ray, Katherine A. Edmonds, Lauren D. Palmer, Eric P. Skaar, David P. Giedroc
Article
Biophysics
Katherine A. Edmonds, Yifan Zhang, Daniel J. Raines, Anne-K Duhme-Klair, David P. Giedroc
BIOMOLECULAR NMR ASSIGNMENTS
(2020)
Article
Microbiology
Reece J. Knippel, Aaron G. Wexler, Jeanette M. Miller, William N. Beavers, Andy Weiss, Valerie de Crecy-Lagard, Katherine A. Edmonds, David P. Giedroc, Eric P. Skaar
CELL HOST & MICROBE
(2020)
Review
Microbiology
Matthew R. Jordan, Jiefei Wang, Daiana A. Capdevila, David P. Giedroc
CURRENT OPINION IN MICROBIOLOGY
(2020)
Article
Biotechnology & Applied Microbiology
Jaeyoung K. Jung, Khalid K. Alam, Matthew S. Verosloff, Daiana A. Capdevila, Morgane Desmau, Phillip R. Clauer, Jeong Wook Lee, Peter Q. Nguyen, Pablo A. Pasten, Sandrine J. Matiasek, Jean-Francois Gaillard, David P. Giedroc, James J. Collins, Julius B. Lucks
NATURE BIOTECHNOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Daiana A. Capdevila, Brenna J. C. Walsh, Yifan Zhang, Christopher Dietrich, Giovanni Gonzalez-Gutierrez, David P. Giedroc
Summary: Structural and kinetic analyses of the transcriptional repressor protein SqrR reveal its persulfide selectivity mechanism, shedding light on the coordinated regulation function of cysteine thiol-based transcriptional regulators in cellular redox homeostasis.
NATURE CHEMICAL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Giuliano T. Antelo, Alejandro J. Vila, David P. Giedroc, Daiana A. Capdevila
Summary: The molecular evolution of the adaptive response at the host-pathogen interface, known as an 'arms race,' involves strategies employed by the innate immune system to starve microbes of metals, countered by pathogens maintaining access to metal ions. Recent exploration of how evolution repurposes host and pathogen proteins to perform new functions is discussed, with a focus on metalloproteins restricting bacterial access to transition metals. Coevolution with bacterial metal acquisition systems and the evolution of metallo-?-lactamases in the context of host-imposed nutritional immunity are also examined.
TRENDS IN MICROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Joseph N. Fakhoury, Yifan Zhang, Katherine A. Edmonds, Mauro Bringas, Justin L. Luebke, Giovanni Gonzalez-Gutierrez, Daiana A. Capdevila, David P. Giedroc
Summary: CstR is a protein that senses persulfides and regulates bacterial response to hydrogen sulfide and other oxidized reactive sulfur species. Research suggests that the specificity of CstRs to different oxidants is determined by their sequence, structural, and kinetic features.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Andy Weiss, Caitlin C. Murdoch, Katherine A. Edmonds, Matthew R. Jordan, Andrew J. Monteith, Yasiru R. Perera, Aslin M. Rodriguez Nassif, Amber M. Petoletti, William N. Beavers, Matthew J. Munneke, Sydney L. Drury, Evan S. Krystofiak, Kishore Thalluri, Hongwei Wu, Angela R. S. Kruse, Richard D. DiMarchi, Richard M. Caprioli, Jeffrey M. Spraggins, Walter J. Chazin, David P. Giedroc, Eric P. Skaar
Summary: This study reveals the existence of a conserved COG0523 protein family in vertebrates and assigns them an important role in regulating cellular zinc homeostasis.
Article
Microbiology
Erin R. Green, Joseph N. Fakhoury, Andrew J. Monteith, Hualiang Pi, David P. Giedroc, Eric P. Skaar
Summary: This study reveals that Acinetobacter baumannii causes more virulent pneumonia following desiccation and identifies the genetic requirements for desiccation. The disruption of Lon protease enhances desiccation tolerance, while bacterial hydrophilins DtpA and DtpB play a crucial role in this process.
CELL HOST & MICROBE
(2022)
Article
Biochemistry & Molecular Biology
Yifan Zhang, Julia E. Martin, Katherine A. Edmonds, Malcolm E. Winkler, David P. Giedroc
Summary: The novel virulence associated Rrf2-family transcriptional repressor SifR regulates genes involved in iron uptake and stress response in Streptococcus pneumoniae, providing insight into how the bacterium acquires iron sources in the host environment. This study sheds light on the mechanisms by which the pathogen adapts to oxidative stress and utilizes catechol-derived iron sources for survival.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Brenna J. C. Walsh, Sofia Soares Costa, Katherine A. Edmonds, Jonathan C. Trinidad, Federico M. Issoglio, Jose A. Brito, David P. Giedroc
Summary: Hydrogen sulfide (H2S) is a cytoprotective agent used by bacteria in response to stress, and this study found that exogenous sulfide alters protein abundance and metabolic reactions in the gut microorganism Enterococcus faecalis, potentially affecting fatty acid pathways.
Article
Biochemistry & Molecular Biology
Katherine A. Edmonds, Matthew R. Jordan, David P. Giedroc
Summary: This study uses genomic enzymology tools to analyze over 80,000 sequences related to zinc metallochaperones, revealing multiple distinct clusters including characterized and uncharacterized COG0523 proteins. Through the analysis of these clusters, new perspectives on COG0523 proteins as cellular reporters of nutrient stress induced by zinc limitation are discussed.
Article
Biology
Brenna J. C. Walsh, David P. Giedroc
Summary: Hydrogen sulfide has been found to play a crucial role in bacterial cytoprotection against host immune response, possibly through the formation of reactive sulfur species derived from H2S. A new analytical method has been developed and successfully applied to studying protein persulfidation in bacterial cells, particularly in a major human pathogen. This method allows quantification and identification of persulfidation sites in the proteome, which may serve as regulatory modifications that can be validated through biochemical studies.