Article
Biochemistry & Molecular Biology
Hongnan Liu, Yuwei Zhu, Zebin Lu, Zhiwei Huang
Summary: Bacteriophages have evolved anti-CRISPR proteins (Acrs) to evade the prokaryotic adaptive immune system, and Acrs can serve as switches to regulate gene editing. The crystal structure of the AcrIIA14-SauCas9-sgRNA-dsDNA complex reveals the molecular basis for AcrIIA14 recognition and inhibition, with AcrIIA14 binding to a non-conserved region of SauCas9 HNH domain. This binding triggers conformational allostery in the HNH domain and L1 linker, enhancing the inhibitory ability of AcrIIA14.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Marian S. Vogt, Roi R. Ngouoko Nguepbeu, Michael K. F. Mohr, Sonja-Verena Albers, Lars-Oliver Essen, Ankan Banerjee
Summary: The study characterized a CYTH ortholog from the crenarchaeote Sulfolobus acidocaldarius, showing its inability to produce cyclic nucleotides and displaying classical triphosphatase activity. Structural analysis revealed conformational dynamics and feedback inhibition in SaTTM, providing a molecular basis for distinguishing CYTH orthologs with phosphatase activities from class IV adenylyl cyclases.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Oncology
Nezihi Murat Karabacak, Yu Zheng, Taronish D. Dubash, Risa Burr, Douglas S. Micalizzi, Ben S. Wittner, Maoxuan Lin, Devon F. Wiley, Valentine Comaills, Erin Emmons, Kira L. Niederhoffer, Uyen Ho, Jacob Ukleja, Dante Che, Hannah Stowe, Linda T. Nieman, Wilhelm Haas, Shannon L. Stott, Michael S. Lawrence, David T. Ting, David T. Miyamoto, Daniel A. Haber, Mehmet Toner, Shyamala Maheswaran
Summary: Single-cell mass cytometry analyses provide insights into the differences in kinase activities across tumor compartments and cell states, which contribute to heterogeneous responses to targeted therapies.
Article
Biochemistry & Molecular Biology
Helen Bergquist, Raviteja Inturi, Rula Zain, Tanel Punga
Summary: RNA molecules can form specific RNA triplex structures, and the investigation on HAdV-4 VA RNAI suggests that it can potentially adopt a biologically relevant triplex structure, which plays a critical role in virus growth and development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Yuta Tsukamoto, Takahiro Hiono, Shintaro Yamada, Keita Matsuno, Aileen Faist, Tobias Claff, Jianyu Hou, Vigneshwaran Namasivayam, Anja vom Hemdt, Satoko Sugimoto, Jin Ying Ng, Maria H. Christensen, Yonas M. Tesfamariam, Steven Wolter, Stefan Juranek, Thomas Zillinger, Stefan Bauer, Takatsugu Hirokawa, Florian I. Schmidt, Georg Kochs, Masayuki Shimojima, Yi-Shuian Huang, Andreas Pichlmair, Beate M. Kuemmerer, Yoshihiro Sakoda, Martin Schlee, Linda Brunotte, Christa E. Mueller, Manabu Igarashi, Hiroki Kato
Summary: Scientists have discovered the importance of host RNA modification in the initiation of influenza virus replication. They found that a derivative of a natural product called TFMT can inhibit this modification and restrict influenza virus replication. TFMT acts synergistically with approved anti-influenza drugs.
Article
Biochemistry & Molecular Biology
Areej Abuhammad, Nicola Laurieri, Alistair Rice, Edward D. Lowe, Nisha Singh, Saleem M. Naser, Samer S. Ratrout, Grant C. Churchill
Summary: Bipolar disorder is a major psychiatric disorder with cognitive impairment and a high suicide rate. Lithium is the frontline therapy, but it has severe side effects. Ebselen, an anti-inflammatory drug, may be an alternative treatment for bipolar disorder by inhibiting IMPase1. However, the exact mechanism of ebselen's action in inhibiting IMPase1 is unclear.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Sandra Schilbach, Shintaro Aibara, Christian Dienemann, Frauke Grabbe, Patrick Cramer
Summary: This study reveals the high-resolution structure of the transcription initiation complex and the mechanism of DNA opening, crucial for promoter-initiated transcription. TFIIE facilitates initiation by supporting the clamp head loop and regulating the TFIIH translocase.
Article
Multidisciplinary Sciences
Azadeh Shahsavar, Peter Stohler, Gleb Bourenkov, Iwan Zimmermann, Martin Siegrist, Wolfgang Guba, Emmanuel Pinard, Steffen Sinning, Markus A. Seeger, Thomas R. Schneider, Roger J. P. Dawson, Poul Nissen
Summary: This study utilized synthetic single-domain antibodies and serial synchrotron crystallography to determine the structure of GlyT1 in complex with an inhibitor, revealing that the inhibitor locks GlyT1 in an inward-open conformation and binds at the intracellular gate of the release pathway. These findings define the mechanism of inhibition and provide insights for the rational design of new, clinically efficacious GlyT1 inhibitors.
Article
Biology
Alison H. Affinati, Paul Sabatini, Cadence True, Abigail J. Tomlinson, Melissa Kirigiti, Sarah R. Lindsley, Chien Li, David P. Olson, Paul Kievit, Martin G. Myers, Alan C. Rupp
Summary: Research has identified multiple clusters of VMH neurons in both mouse and macaque tissues, divided into six main classes with good cross-species conservation. The expression of leptin receptor (Lepr) marks a specific category of VMH neurons.
Article
Multidisciplinary Sciences
Yange Niu, Rui Liu, Chengcheng Guan, Yuan Zhang, Zhixing Chen, Stefan Hoerer, Herbert Nar, Lei Chen
Summary: Inhibition of hSGLT2 by small-molecule inhibitors such as empagliflozin enhances glucose excretion, which is widely used in clinical settings to manage blood glucose levels in patients with type 2 diabetes. The cryogenic electron microscopy structure of the hSGLT2-MAP17 complex in the empagliflozin-bound state reveals key interactions and provides a basis for future development of new inhibitors targeting these transporters.
Article
Biochemistry & Molecular Biology
Daniel Krochmal, Yaming Shao, Nan-Sheng Li, Saurja DasGupta, Sandip A. Shelke, Deepak Koirala, Joseph A. Piccirilli
Summary: Ribozymes that react with small-molecule probes have important applications in transcriptomics and chemical biology. This study focuses on a self-alkylating ribozyme and reports its crystal structures, showing a hook-shaped conformation.
NATURE CHEMICAL BIOLOGY
(2022)
Article
Medicine, General & Internal
Andrew J. Shih, Robert P. Adelson, Himanshu Vashistha, Houman Khalili, Ashima Nayyar, Radha Puran, Rixsi Herrera, Prodyot K. Chatterjee, Annette T. Lee, Alexander M. Truskinovsky, Kristine Elmaliki, Margaret DeFranco, Christine N. Metz, Peter K. Gregersen
Summary: This study found significant differences in endometrial tissues between endometriosis cases and controls. The controls had more proliferating uterine natural killer cells and decidualized endometrial stromal cells, while the cases had more cells expressing inflammatory and senescent phenotypes.
Article
Biotechnology & Applied Microbiology
Chase A. Weidmann, Anthony M. Mustoe, Parth B. Jariwala, J. Mauro Calabrese, Kevin M. Weeks
Summary: The newly developed RNP-MaP method allows for mapping cooperative interactions among multiple proteins bound to single RNA molecules at nucleotide resolution, revealing characteristics of RNA-protein interaction networks.
NATURE BIOTECHNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Rafael Molina, Anne Louise Gron Jensen, Javier Marchena-Hurtado, Blanca Lopez-Mendez, Stefano Stella, Guillermo Montoya
Summary: Type III CRISPR-Cas effector systems detect foreign RNA and trigger cell dormancy or death. Standalone ring nucleases downregulate the immune response by degrading cA, thus controlling the cell antiviral state.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Yingxin Cao, Laiyi Fu, Jie Wu, Qinke Peng, Qing Nie, Jing Zhang, Xiaohui Xie
Summary: In this study, we propose a deep learning framework called SAILERX for efficient, robust, and flexible analysis of multi-modal single-cell data. SAILERX utilizes invariant representation learning and multimodal data alignment mechanism to handle noise, integrate information, and provide various downstream analysis functions.
NUCLEIC ACIDS RESEARCH
(2022)