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Biochemistry & Molecular Biology
Toru Sengoku, Masaaki Shiina, Kae Suzuki, Keisuke Hamada, Ko Sato, Akiko Uchiyama, Shunsuke Kobayashi, Asako Oguni, Hayato Itaya, Kota Kasahara, Hirotomo Moriwaki, Chiduru Watanabe, Teruki Honma, Chikako Okada, Shiho Baba, Tsutomu Ohta, Hozumi Motohashi, Masayuki Yamamoto, Kazuhiro Ogata
Summary: This study reveals the crystal structures of Nrf2/NFE2L2, a CNC family protein, in complex with MafG and CsMBE. The CNC motif restricts the conformation of crucial amino acids, leading to enhanced DNA binding affinity. The CNC-sMaf heterodimer competes with the sMaf homodimer on target genes.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Medicine, Research & Experimental
Liangkai Cheng, Huihui Wang, Shehan Li, Zhongqiu Liu, Caiyan Wang
Summary: This study revealed the significance of Nrf2(Thr80) and Nrf2(Pro85) in the Keap1-Nrf2 interaction, as well as the impact of Keap1 mutations on Nrf2 binding. These findings provide important insights for further understanding the role of the Keap1/Nrf2 signaling pathway in cancer development.
Article
Chemistry, Multidisciplinary
Louise Bryan, Saurabh Awasthi, Yuanjie Li, Peter Niraj Nirmalraj, Sandor Balog, Jerry Yang, Michael Mayer
Summary: Researchers have developed a new method to fluorescently label Tau protein at its C-terminus without disturbing the microtubule binding region, allowing for the study of pathological protein aggregation. The C-terminal modification of Tau protein was found to have no significant impact on its properties, such as aggregation kinetics, secondary structure, and fibril morphology.
Article
Neurosciences
Kiki J. Chen, Ryan Yoshimura, Clarissa Adriana Edmundo, Tri Minh Truong, Olivier Civelli, Amal Alachkar, Geoffrey W. Abbott
Summary: By investigating the GABA binding site that activates KCNQ3, it was found that this direct interaction has significant effects on mouse behavior, especially in regulating nociception and stress responses. This finding provides new targets for treating neurological and psychiatric disorders.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Matthew McCallum, Anna De Marco, Florian Lempp, M. Alejandra Tortorici, Dora Pinto, Alexandra C. Walls, Martina Beltramello, Alex Chen, Zhuoming Liu, Fabrizia Zatta, Samantha Zepeda, Julia di Iulio, John E. Bowen, Martin Montiel-Ruiz, Jiayi Zhou, Laura E. Rosen, Siro Bianchi, Barbara Guarino, Chiara Silacci Fregni, Rana Abdelnabi, Shi-Yan Caroline Foo, Paul W. Rothlauf, Louis-Marie Bloyet, Fabio Benigni, Elisabetta Cameroni, Johan Neyts, Agostino Riva, Gyorgy Snell, Amalio Telenti, Sean P. J. Whelan, Herbert W. Virgin, Davide Corti, Matteo Samuele Pizzuto, David Veesler
Summary: The study identifies 41 human monoclonal antibodies that recognize the N-terminal domain of the SARS-CoV-2 spike protein and exhibit strong neutralizing activity. These antibodies inhibit cell-to-cell fusion, activate effector functions, and protect animals from virus challenge, highlighting the importance of NTD-specific neutralizing antibodies for protective immunity and vaccine development. Several SARS-CoV-2 variants with mutations in the NTD supersite suggest ongoing selective pressure on the virus.
Article
Pharmacology & Pharmacy
Wen Li, Xiaomu Wang, Xiandong Meng, Wen Jiang, Dong Wei
Summary: The study found that the intracellular N-terminus of ASIC1a plays a significant role in membrane expression and gate opening. The entire N-terminus of ASICs is involved in the membrane expression of ASIC1a, and five amino acid residues (amino acid 16-20) are crucial for the gate opening mechanism.
MOLECULAR PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Maria Rosa Beccia, Sandrine Sauge-Merle, Nicolas Bremond, David Lemaire, Pierre Henri, Christine Battesti, Philippe Guilbaud, Serge Crouzy, Catherine Berthomieu
Summary: Uranyl-protein interactions play a significant role in uranyl trafficking or toxicity to cells. This study investigates the thermodynamic properties of uranyl interaction with different binding sites on calmodulin (CaM) and the whole CaM N-terminal domain. The binding affinity and thermodynamic contributions vary between different sites, and phosphorylation enhances the uranyl-binding affinity and cooperativity. A structural role of phosphorylation in affinity modulation is suggested by the obtained structural model.
Article
Biology
Santana Royan, Bernard Gutmann, Catherine Colas des Francs-Small, Suvi Honkanen, Jason Schmidberger, Ashley Soet, Yueming Kelly Sun, Lilian Vincis Pereira Sanglard, Charles S. Bond, Ian Small
Summary: RNA editing in plants is carried out by PPR proteins, and a synthetic editing factor using PPR motifs has been successfully designed and demonstrated high specificity. This study paves the way for the design and application of programmable RNA editing factors based on plant PPR proteins.
COMMUNICATIONS BIOLOGY
(2021)
Article
Cell Biology
Matteo Bosso, Christina M. Sturzel, Dorota Kmiec, Smitha Srinivasachar Badarinarayan, Elisabeth Braun, Jumpei Ito, Kei Sato, Beatrice H. Hahn, Konstantin M. J. Sparrer, Daniel Sauter, Frank Kirchhoff
Summary: Subtype C HIV-1 strains, the most prevalent worldwide, possess an additional third NF-kappa B binding site in the LTR promoter that confers resistance to nuclear PYHIN proteins, which helps explain their dominance.
Article
Multidisciplinary Sciences
Susan M. Mitchell, Morven Graham, Xinran Liu, Ralf M. Leonhardt
Summary: The PMEL protein forms a functional amyloid matrix in melanosomes for melanin deposition, with the N-terminal domain playing a critical role in amyloid formation and assembly morphology.
SCIENTIFIC REPORTS
(2021)
Article
Chemistry, Multidisciplinary
Ammar Ammar, Rachel Cavill, Chris Evelo, Egon Willighagen
Summary: Protein mutations, especially in the binding site, can impact drug response. Experimental screening is time-consuming and expensive, so computational approaches are valuable in guiding these experiments.
JOURNAL OF CHEMINFORMATICS
(2023)
Article
Chemistry, Multidisciplinary
Ammar Ammar, Rachel Cavill, Chris Evelo, Egon Willighagen
Summary: A large database of 0.6 million mutated binding site protein-ligand complexes, called PSnpBind, has been constructed to provide a reference dataset for studying the effects of natural variants on drug targets. This database is important for developing machine learning algorithms and studying protein-ligand affinity.
JOURNAL OF CHEMINFORMATICS
(2022)
Article
Biochemistry & Molecular Biology
Sachiko Toma-Fukai, Yuto Sawada, Ayako Maeda, Hikaru Shimizu, Toshiharu Shikanai, Mizuki Takenaka, Toshiyuki Shimizu
Summary: The activation mechanism of DYW1-like proteins is achieved through complementation of the DYW domain and reconstitution of the substrate-binding pocket. This provides structural insight into the activation mechanism of cytidine deaminase.
Article
Biochemistry & Molecular Biology
Takuya Murata, Genta Ito, Naoko Utsunomiya-Tate
Summary: Tau, a microtubule-binding protein, is a major component of neurofibrillary tangles in Alzheimer's disease. D-isomerized Asp accumulation in Tau affects fibril morphology and weakens the potency of Tau aggregation inhibitors. This study provides insights into the impact of D-isomerization on Tau and its implications in Alzheimer's disease pathogenesis.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Cell Biology
James H. Baraniak, Yandong Zhou, Robert M. Nwokonko, Michelle R. Jennette, Sarah A. Kazzaz, Jazmin M. Stenson, Abigale L. Whitsell, Youjun Wang, Mohamed Trebak, Donald L. Gill
Summary: The study reveals that the interaction between M4x peptides in Orai channels and STIM1 protein can block Ca2+ signal transduction and affect the coupling between STIM and Orai proteins, thereby regulating the cell's Ca2+ signaling pathway.