Article
Medicine, General & Internal
Roxane Verdikt, Maryam Bendoumou, Sophie Bouchat, Lorena Nestola, Alexander O. Pasternak, Gilles Darcis, Veronique Avettand-Fenoel, Caroline Vanhulle, Amina Ait-Ammar, Marion Santangelo, Estelle Plant, Valentin Le Douce, Nadege Delacourt, Coca Necsoi, Francis Corazza, Caroline Pereira Bittencourt Passaes, Christian Schwartz, Martin Bizet, Francois Fuks, Asier Saez-Cirion, Christine Rouzioux, Stephane De Wit, Ben Berkhout, Virginie Gautier, Olivier Rohr, Carine Van Lint
Summary: This study uncovers specific demethylation CpG signatures induced by 5-AzadC in the HIV-1 promoter and reveals the recruitment of UHRF1 to the HIV-1 promoter. It demonstrates the role of UHRF1 in the epigenetic repression of the latent viral promoter.
Article
Materials Science, Biomaterials
Daria Sanchugova, Aleksandra Kusova, Aydar Bikmullin, Vladimir Klochkov, Dmitriy Blokhin
Summary: SEM1(86-107) peptide is a cleavage product expressed in seminal vesicles, forming amyloid fibrils in semen and potentially increasing HIV infectivity. The spatial structure of SEM1(86-107) was studied using NMR and CD spectroscopy, revealing regions with random coil conformations. Analysis showed that specific fragments within the peptide are responsible for the fibrillation process.
Article
Virology
Kannan Balakrishnan, Ananda Ayyappan Jaguva Vasudevan, Krishnaveni Mohareer, Tom Luedde, Carsten Muenk, Sharmistha Banerjee
Summary: The study showed that Staufen-2 interacts with HIV-1 Gag, boosting viral infectivity by being incorporated into virions. Additionally, Staufen-2 may interact with other host factors, influencing the infectivity and population dynamics of the virus.
Article
Biochemistry & Molecular Biology
Eric Barklis, Ayna Alfadhli, Jennifer E. Kyle, Lisa M. Bramer, Kent J. Bloodsworth, Robin Lid Barklis, Hans C. Leier, R. Max Petty, Iris D. Zelnik, Thomas O. Metz, Anthony H. Futerman, Fikadu G. Tafesse
Summary: Research shows that CerS2 deficiency alters the lipid composition, specifically inhibiting the receptor binding or fusion of HIV-1 Env during infection.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Plant Sciences
Yanwei Wang, Jing Sun, Chen Deng, Shouzhen Teng, Guoxin Chen, Zhenhua Chen, Xuean Cui, Thomas P. Brutnell, Xiao Han, Zhiguo Zhang, Tiegang Lu
Summary: This study identified the role of the SEM1 gene in regulating sucrose transport in rice by analyzing two mesophyll starch excess mutants. Through characterization and experimental validation, the relationship between sucrose and vascular cell development was revealed.
Article
Oncology
Chuntao Li, Bo Chen, Junxia Zhang, Jingxuan Yang, Muzi Guo, Yu Ren, Zhijun Zhou, Kar-Ming Fung, Min Li, Liyang Zhang, Zhixiong Liu
Summary: SEM1 is highly expressed in gliomas and correlated with malignant features and poor prognosis. SEM1 plays a critical role in the proliferation, apoptosis, invasion, and migration of glioma cells through regulating the PI3K-Akt pathway. The SEM1 malignant regulatory network shows significant importance for the prognosis and treatment of gliomas.
Article
Multidisciplinary Sciences
Shumei Wang, Li Zhao, Xiaowei Zhang, Jingjing Zhang, Hong Shang, Guoxin Liang
Summary: This study reveals that neuropilin-1 (NRP-1) is highly expressed in macrophages and dendritic cells (DCs) but not CD4(+) T cells. NRP-1 functions as an antiviral protein, inhibiting the infectivity of HIV-1 by reducing the ability of the virions to attach to target cells.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Daria A. Osetrina, Aleksandra M. Kusova, Aydar G. Bikmullin, Evelina A. Klochkova, Aydar R. Yulmetov, Evgenia A. Semenova, Timur A. Mukhametzyanov, Konstantin S. Usachev, Vladimir V. Klochkov, Dmitriy S. Blokhin
Summary: This study describes the involvement of four peptide fragments of Semenogelin 1 (SEM1) in fertilization and amyloid formation processes. The amyloid formation of SEM1(45-107) was observed immediately after purification, while SEM1(49-107) did not show this behavior. The difference in amyloid-forming behavior between the two peptides can be explained by the presence of a structured helix at the N-terminus of SEM1(45-107).
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Fu-Hsien Yu, Kuo-Jung Huang, Chin-Tien Wang
Summary: The p6* region in HIV-1 Gag-Pol plays a crucial role in PR activation. Mutations at p6* F8 result in reduced virus infectivity due to impaired PR maturation and RT packaging.
Article
Virology
Ayna Alfadhli, CeAnn Romanaggi, Robin Lid Barklis, Ilaria Merutka, Timothy A. Bates, G. Tafesse, Eric Barklis
Summary: Specific nanobodies can be used for detecting HIV-1 CA with sensitivity and specificity. NTD-specific nanobodies can efficiently assemble into virions, while CTD-specific nanobodies reduce virus release and infectivity. These findings suggest the potential of Gag-targeted nanobodies for inhibiting HIV-1.
Article
Multidisciplinary Sciences
Jing Zhao, Alan Blayney, Xiaorong Liu, Lauren Gandy, Weihua Jin, Lufeng Yan, Jeung-Hoi Ha, Ashley J. Canning, Michael Connelly, Chao Yang, Xinyue Liu, Yuanyuan Xiao, Michael S. Cosgrove, Sozanne R. Solmaz, Yingkai Zhang, David Ban, Jianhan Chen, Stewart N. Loh, Chunyu Wang
Summary: Epigallocatechin gallate (EGCG) in green tea induces apoptosis in cancerous cells through a direct interaction with the tumor suppressor p53, inhibiting p53 ubiquitination by its regulatory E3 ligase MDM2 and stabilizing p53 for anti-tumor activity.
NATURE COMMUNICATIONS
(2021)
Article
Materials Science, Multidisciplinary
Qiang Peng, Ruoping Wang, Qian Zhang, Honghan Yuan, Xiaofang Luo, Wanzhen Lin, Junpeng Shi, Liang Song, Maochun Hong, Yun Zhang
Summary: The emergence of multidrug-resistant bacteria poses a serious threat to human health, and developing new antibacterial strategies is crucial. Recently, a pH-responsive targeted nanomaterial called ZEI@GCS has shown great potential in improving the bioavailability of the antibacterial agent EGCG. It also allows for evaluating the therapeutic outcome in mice.
ACS MATERIALS LETTERS
(2023)
Review
Biochemistry & Molecular Biology
Veronna Marie, Michelle Lucille Gordon
Summary: The HIV-1 Gag polyprotein, originally believed to only contribute to the physical nature of the virus, has been found to have multiple roles in viral replication and functionality. It can mediate its own trafficking, interact with host factors, and aid in viral genome packaging. It has also been associated with drug resistance and treatment failure.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Virology
Malvina Schatz, Laetitia Marty, Camille Ounadjela, Phuoc Bao Viet Tong, Ilaria Cardace, Clement Mettling, Pierre-Emmanuel Milhiet, Luca Costa, Cedric Godefroy, Martine Pugniere, Jean-Francois Guichou, Jean-Michel Mesnard, Mickael Blaise, Bruno Beaumelle
Summary: A tripartite complex consisting of Tat, CypA, and CA was found to be assembled in HIV-1-infected cells, allowing Tat to be encapsidated into HIV virions. Encapsidated Tat is required for efficient viral transcription and enhanced infectivity.
JOURNAL OF VIROLOGY
(2023)
Article
Cell Biology
Qingqing Chai, Sunan Li, Morgan K. Collins, Rongrong Li, Iqbal Ahmad, Silas F. Johnson, Dylan A. Frabutt, Zhichang Yang, Xiaojing Shen, Liangliang Sun, Jian Hu, Judd F. Hultquist, B. Matija Peterlin, Yong-Hui Zheng
Summary: The study reveals that HIV-1 negative factor (Nef) protein antagonizes SERINC5 by redirecting it to endosomes and lysosomes for degradation through a kinase complex involving cyclin K (CycK) and cyclin-dependent kinase 13 (CDK13). Phosphorylation of serine 360 (S360) in SERINC5 by CycK/CDK13 is crucial for Nef-mediated downregulation of SERINC5 and its antiviral activity. Interaction between Nef and SERINC5 is enhanced by S360 phosphorylation, leading to SERINC5 destruction by the endocytic machinery.
Article
Hematology
Julia T. Warren, Ryan R. Cupo, Peeradol Wattanasirakul, David H. Spencer, Adam E. Locke, Vahagn Makaryan, Audrey Anna Bolyard, Merideth L. Kelley, Natalie L. Kingston, James Shorter, Christine Bellanne-Chantelot, Jean Donadieu, David C. Dale, Daniel C. Link
Summary: Genetic analysis of patients with congenital neutropenia revealed an association between CLPB variants and the disease. CLPB variants obstruct the differentiation of granulocytes and increase apoptosis, contributing to the development of neutropenia. This study provides new insights into the diagnosis and treatment of congenital neutropenia.
Review
Biochemistry & Molecular Biology
Hana M. Odeh, Charlotte M. Fare, James Shorter
Summary: The article discusses the role of nuclear import receptors (NIRs) in nuclear transport and their ability to chaperone and disaggregate NLS-bearing clients in the cytoplasm. It highlights the finding that NIRs can also antagonize aberrant interactions and toxicity of proteins associated with neurodegenerative diseases. Additionally, NIR family members are shown to prevent and reverse liquid-liquid phase separation of specific clients independent of nuclear localization signals (NLS). Strategies to enhance NIR activity or expression for the treatment of neurodegenerative disorders are also discussed.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Kevin Rhine, Morgan Dasovich, Joseph Yoniles, Mohsen Badiee, Sophie Skanchy, Laura R. Ganser, Yingda Ge, Charlotte M. Fare, James Shorter, Anthony K. L. Leung, Sua Myong
Summary: This study demonstrates how Poly(ADP-ribose) (PAR) triggers condensation of FUS at a low concentration, and reveals a different mode of interaction between PAR and FUS compared to RNA.
Article
Cell Biology
Ryan R. Cupo, Alexandrea N. Rizo, Gabriel A. Braun, Eric Tse, Edward Chuang, Kushol Gupta, Daniel R. Southworth, James Shorter
Summary: The high-resolution structure of Skd3-substrate complex is reported, revealing the mechanism of Skd3 protein disaggregation and its association with disease inheritance patterns.
Article
Biochemistry & Molecular Biology
Charlotte M. Fare, Kevin Rhine, Andrew Lam, Sua Myong, James Shorter
Summary: KapP2 is a nuclear-import receptor that transports various cytoplasmic cargo, including disease-linked RNA-binding proteins, to the nucleus. These RNA-binding proteins with prion-like domains are associated with degenerative disorders. KapP2 can prevent and reverse aberrant phase transitions of these proteins, providing cytoprotection. The molecular determinants of KapP2's activities are poorly understood, but truncations lacking cargo-binding repeats show reduced activity. HEAT repeats 8 to 20 of KapP2 recapitulate its activity, making them a potential therapeutic target for related disorders.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Steven Boeynaems, Shasha Chong, Jorg Gsponer, Liam Holt, Dragomir Milovanovic, Diana M. Mitrea, Oliver Mueller-Cajar, Bede Portz, John F. Reilly, Christopher D. Reinkemeier, Benjamin R. Sabari, Serena Sanulli, James Shorter, Emily Sontag, Lucia Strader, Jeanne Stachowiak, Stephanie C. Weber, Michael White, Huaiying Zhang, Markus Zweckstetter, Shana Elbaum-Garfinkle, Richard Kriwacki
Summary: Over the past 15 years, a new scientific field called biomolecular condensates has emerged, focusing on the study of membraneless bodies in cells and their roles in biological processes and disease. These condensates are formed through phase separation and have been found to play crucial roles in various cellular functions and disease pathways. Through a week-long workshop, scientists discussed the key questions and insights in this field, including the applications of condensates in synthetic biology and potential therapeutic targeting.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Neurosciences
Bilal Khalil, Deepak Chhangani, Melissa C. Wren, Courtney L. Smith, Jannifer H. Lee, Xingli Li, Christian Puttinger, Chih-Wei Tsai, Gael Fortin, Dmytro Morderer, Junli Gao, Feilin Liu, Chun Kim Lim, Jingjiao Chen, Ching-Chieh Chou, Cara L. Croft, Amanda M. Gleixner, Christopher J. Donnelly, Todd E. Golde, Leonard Petrucelli, Bjorn Oskarsson, Dennis W. Dickson, Ke Zhang, James Shorter, Shige H. Yoshimura, Sami J. Barmada, Diego E. Rincon-Limas, Wilfried Rossoll
Summary: The study found that members of the nuclear import receptor protein family can reduce the formation of pathological TDP-43 aggregates. Using KPNB1 as a model, it was discovered that its activity depends on the prion-like C-terminal region of TDP-43, mediating co-aggregation with nucleoporins such as Nup62. KPNB1 acts as a molecular chaperone in these co-aggregates, reversing the aberrant phase transition of Nup62 and TDP-43.
MOLECULAR NEURODEGENERATION
(2022)
Article
Clinical Neurology
Pedro Ervilha Pereira, Nika Schuermans, Antoon Meylemans, Pontus LeBlanc, Lauren Versluys, Katie E. E. Copley, Jack D. D. Rubien, Christopher Altheimer, Myra Peetermans, Elke Debackere, Olivier Vanakker, Sandra Janssens, Jonathan Baets, Kristof Verhoeven, Martin Lammens, Sofie Symoens, Boel De Paepe, Sami J. J. Barmada, James Shorter, Jan L. L. De Bleecker, Elke Bogaert, Bart Dermaut
Summary: This study identified a TDP-43(p.Trp385IlefsTer10) mutation in a family, which led to the presence of TDP-43-positive inclusions in muscle cells and the development of autosomal dominant rimmed vacuole myopathy. The mutation was found to increase the aggregation propensity of TDP-43, but it was not associated with ALS and FTD.
ACTA NEUROPATHOLOGICA
(2023)
Review
Chemistry, Multidisciplinary
Kevin Rhine, Hana M. Odeh, James Shorter, Sua Myong
Summary: Biomolecular condensates are reversible compartments formed through phase separation, which can be nucleated by post-translational modifications like ADP-ribosylation. Poly(ADP-ribose) (PAR) chains, transient modifications with short turnover rates, play a crucial role in granule formation and are associated with neurodegenerative diseases. This review explores the synthesis, regulation, structure, chemistry, and protein interactions of PAR, as well as recent progress in understanding its role in phase separation and potential as a target for neurodegenerative disease treatments.
Review
Genetics & Heredity
Katie E. Copley, James Shorter
Summary: Repetitive elements (REs), including transposable elements (TEs) and satellites, play a significant role in aging and neurodegenerative disorders. Changes in RE expression, retrotransposition, and chromatin microenvironment can affect lifespan, neurodegeneration, memory, and movement. REs can cause these effects through DNA damage, protein sequestration, insertional mutagenesis, and inflammation. The study focuses on different TE families and their interaction with factors like TDP-43 and the siRNA and piRNA systems.
TRENDS IN GENETICS
(2023)
Editorial Material
Chemistry, Multidisciplinary
Sua Myong, James Shorter
Article
Biochemistry & Molecular Biology
Korrie L. Mack, Hanna Kim, Edward M. Barbieri, Jiabei Lin, Sylvanne Braganza, Meredith E. Jackrel, Jamie E. Denizio, Xiaohui Yan, Edward Chuang, Amber Tariq, Ryan R. Cupo, Laura M. Castellano, Kim A. Caldwell, Guy A. Caldwell, James Shorter
Summary: By engineering substrate-specific variants of the Hsp104 protein, researchers have developed a way to mitigate the toxic misfolding of proteins associated with fatal neurodegenerative disorders. These variants selectively suppress the toxicity of α-synuclein while not affecting the toxicity of TDP-43 or FUS. The specific variants reduce dopamine neuron degeneration more effectively in a Parkinson's disease model compared to non-specific variants.
Article
Biology
Rubika Balendra, Igor Ruiz de los Mozos, Hana M. Odeh, Idoia Glaria, Carmelo Milioto, Katherine M. Wilson, Agnieszka M. Ule, Martina Hallegger, Laura Masino, Stephen Martin, Rickie Patani, James Shorter, Jernej Ule, Adrian M. Isaacs
Summary: An intronic GGGGCC repeat expansion in C9orf72 is a common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia. Poly(GA), poly(GR), and poly(PR) dipeptide repeat proteins generated from the repeats are implicated in neurodegeneration. In this study, we performed CLIP analysis and found that poly(PR) binds to nearly 600 RNAs, with enrichment of the sequence GAAGA at the binding sites. In vitro experiments showed that poly(GAAGA) RNA has a higher affinity for poly(PR) and induces its phase separation into condensates.
LIFE SCIENCE ALLIANCE
(2023)
Correction
Multidisciplinary Sciences
Julien Couthouis, Michael P. Hart, James Shorter, Mariely DeJesus-Hernandez, Renske Erion, Rachel Oristano, Annie X. Liu, Daniel Ramos, Niti Jethava, Divya Hosangadi, James Epstein, Ashley Chiang, Zamia Diaz, Tadashi Nakaya, Fadia Ibrahim, Hyung-Jun Kim, Jennifer A. Solski, Kelly L. Williams, Jelena Mojsilovic-Petrovic, Caroline Ingre, Kevin Boylan, Neill R. Graff-Radford, Dennis W. Dickson, Dana Clay-Falcone, Lauren Elman, Leo McCluskey, Robert Greene, Robert G. Kalb, Virginia M. -Y. Lee, John Q. Trojanowski, Albert Ludolph, Wim Robberecht, Peter M. Andersen, Garth A. Nicholson, Ian P. Blair, Oliver D. King, Nancy M. Bonini, Vivianna Van Deerlin, Rosa Rademakers, Zissimos Mourelatos, Aaron D. Gitler
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Chemistry, Multidisciplinary
Tatjana Weil, Abbna Kirupakaran, My-Hue Le, Philipp Rebmann, Joel Mieres-Perez, Leila Issmail, Carina Conzelmann, Janis A. Mueller, Lena Rauch, Andrea Gilg, Lukas Wettstein, Ruediger Gross, Clarissa Read, Tim Bergner, Sandra Axberg Palsson, Nadja Uhlig, Valentina Eberlein, Heike Woell, Frank-Gerrit Klaerner, Steffen Stenger, Beate M. Kuemmerer, Hendrik Streeck, Giorgio Fois, Manfred Frick, Peter Braubach, Anna-Lena Spetz, Thomas Grunwald, James Shorter, Elsa Sanchez-Garcia, Thomas Schrader, Jan Muench
Summary: This study discovered that a class of drugs called molecular tweezers can disrupt the envelope of SARS-CoV-2 and render the virus non-infectious. By modifying the molecular structure, researchers identified a series of advanced molecular tweezers that showed enhanced ability to destroy lipid bilayers and suppress SARS-CoV-2 infection. These potentiated tweezers demonstrated activity against various viruses, including respiratory syncytial virus, influenza, and measles viruses, in addition to SARS-CoV-2. The inhibitory effects of the advanced tweezers against respiratory syncytial virus and SARS-CoV-2 were also validated in mice. Therefore, these broad-spectrum antiviral agents have great potential for clinical development in combating highly pathogenic viruses.