Article
Microbiology
Safia S. Aljedani, Tyler J. Liban, Karen Tran, Ganesh Phad, Suruchi Singh, Viktoriya Dubrovskaya, Pradeepa Pushparaj, Paola Martinez-Murillo, Justas Rodarte, Alex Mileant, Vidya Mangala Prasad, Rachel Kinzelman, Sijy O'Dell, John R. Mascola, Kelly K. Lee, Gunilla B. Karlsson Hedestam, Richard T. Wyatt, Marie Pancera
Summary: Understanding how antibodies target and neutralize specific regions of the HIV-1 envelope glycoprotein is crucial for vaccine development. Structural analysis revealed that vaccine-induced antibodies from different clonal lineages can penetrate the glycan shield to recognize a unique region within the V2 area, leading to potent neutralization of the autologous virus.
Article
Biochemistry & Molecular Biology
Huchen Zhang, Shijie Yi, Yuan Zhang, Zhi Hong
Summary: Asparagine-linked glycosylation (ALG, N-glycosylation) is a common protein modification in eukaryotes, and its mutation can affect the structure and localization of brassinosteroids insensitive 1 (BRI1). The removal of N-154-glycan enhances BRI1 function, while mutations on the N154 site disrupt protein folding and hydrogen bond formation. Additionally, the similarity between N154 and N275 suggests a role for N-glycans in protein conformation and intracellular localization.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Cell Biology
Jeong Hyun Lee, Catherine Nakao, Michael Appel, Amber Le, Elise Landais, Oleksandr Kalyuzhniy, Xiaozhen Hu, Alessia Liguori, Tina-Marie Mullen, Bettina Groschel, Robert K. Abbott, Devin Sok, William R. Schief, Shane Crotty
Summary: Inducing broadly neutralizing antibodies against HIV is challenging, but this study shows that using germline-targeting immunogens can lead to the accumulation of high-affinity antibodies with potent neutralization after a single immunization.
Article
Biochemistry & Molecular Biology
Sana Qausain, Faez Iqbal Khan, Md Khurshid Alam Khan
Summary: 1-Cys peroxiredoxin6 (Prdx6) is a unique and inducible bifunctional enzyme in the mammalian lungs, playing a role in the progression and inhibition of cancer cells. It possesses two distinct active sites for phospholipase A2 and peroxidase activity. The conserved residues surrounding the peroxidase active site, known as second shell residues, include Glu50, Leu71, Ser72, His79, and Arg155. The study aimed to explore the role of Glu50 in the stabilization of the transition state of Prdx6 through mutation analysis and comparative analyses of biochemical, biophysical, and in silico methods. The results demonstrate that Glu50 significantly affects the structure, stability, and active site stabilization of Prdx6.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Biology
Theresa Hwang, Sara S. Parker, Samantha M. Hill, Meucci W. Ilunga, Robert A. Grant, Ghassan Mouneimne, Amy E. Keating
Summary: The study reveals that the protein PCARE has a high specificity for binding to ENAH over paralogs VASP and EVL, inhibiting ENAH-dependent adhesion in cells. PCARE achieves specificity by stabilizing a conformation of the ENAH EVH1 domain that is inaccessible to other family members. The research uncovers a mechanism of interaction specificity that can differentiate highly similar paralogs and provides tools for studying Ena/VASP functions in processes such as cancer cell invasion.
Article
Multidisciplinary Sciences
Camila H. Coelho, Wai Kwan Tang, Martin Burkhardt, Jacob D. Galson, Olga Muratova, Nichole D. Salinas, Thiago Luiz Alves e Silva, Karine Reiter, Nicholas J. MacDonald, Vu Nguyen, Raul Herrera, Richard Shimp, David L. Narum, Miranda Byrne-Steele, Wenjing Pan, Xiaohong Hou, Brittany Brown, Mary Eisenhower, Jian Han, Bethany J. Jenkins, Justin Y. A. Doritchamou, Margery G. Smelkinson, Joel Vega-Rodriguez, Johannes Trueck, Justin J. Taylor, Issaka Sagara, Jonathan P. Renn, Niraj H. Tolia, Patrick E. Duffy
Summary: This study identifies a human monoclonal antibody from Pfs230 vaccinated individuals that can effectively block the transmission of Plasmodium falciparum to mosquitoes in a complement-dependent manner and reacts with the gamete surface.
NATURE COMMUNICATIONS
(2021)
Article
Neurosciences
Hengameh Shams, Atsuko Matsunaga, Qin Ma, Mohammad R. K. Mofrad, Alessandro Didonna
Summary: This study reveals the impact of an overlooked post-translational modification, lysine methylation, on the functionality of neuronal microtubule-associated protein tau. The research shows that methylated tau is more prone to self-assembly into insoluble structures and affects its stabilization activity on microtubule dynamics. Furthermore, methylation plays a role in regulating neuronal differentiation and cell proliferation.
MOLECULAR AND CELLULAR NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Alexander Krah, Bas van der Hoeven, Luuk Mestrom, Fabio Tonin, Kirsten C. C. Knobel, Peter J. Bond, Duncan G. G. McMillan
Summary: The study used molecular dynamics simulations to predict the impact of a residue outside the ATP binding site on ATP binding affinity in the B. subtilis epsilon subunit of the ATP synthase. The predictions were confirmed by experimental point mutations, demonstrating how MD can predict changes in substrate binding sites in simple protein structures. This research sheds light on why seemingly identical epsilon subunits in different ATP synthases have significantly different ATP binding affinities.
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2021)
Article
Microbiology
Juan A. Torres, Rebecca R. Pasquarelli, Peter S. Back, Andy S. Moon, Peter J. Bradley
Summary: The study identifies a novel component of the Toxoplasma gondii IMC, IMC32, which is essential for parasite survival by localizing to developing daughter buds early during endodyogeny. IMC32's localization depends on specific structural domains, and two conserved regions within the C-terminal coiled-coil domains are critical for its function during replication. This provides a potential new therapeutic target for T. gondii and related apicomplexan parasites.
Article
Chemistry, Medicinal
Jana Flegel, Saad Shaaban, Zhi Jun Jia, Britta Schulte, Yilong Lian, Adrian Krzyzanowski, Malte Metz, Tabea Schneidewind, Fabian Wesseler, Anke Flegel, Alisa Reich, Alexandra Brause, Gang Xue, Minghao Zhang, Lara Doetsch, Isabelle D. Stender, Jan-Erik Hoffmann, Rebecca Scheel, Petra Janning, Fraydoon Rastinejad, Dennis Schade, Carsten Strohmann, Andrey P. Antonchick, Sonja Sievers, Pedro Moura-Alves, Slava Ziegler, Herbert Waldmann
Summary: Identification of novel bioactive chemical matter can be achieved through target-agnostic cellular assays and monitoring changes in phenotype followed by target identification. In this study, the enantioselective synthesis of natural product-inspired 8-oxotetrahydroprotoberberines led to the identification of Picoberin, a low picomolar inhibitor of Hedgehog-induced osteoblast differentiation. The molecular target of Picoberin was identified as the aryl hydrocarbon receptor (AhR), and a cross talk between Hedgehog and AhR signaling during osteoblast differentiation was revealed.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Physiology
Matthew L. Rook, Megan Miaro, Tyler Couch, Dana L. Kneisley, Maria Musgaard, David M. MacLean
Summary: Desensitization is a common feature in ASIC ion channels, but the Q276G mutation does not have a significant impact in both human and chicken ASIC1, showing unexpected differences compared to previous findings.
JOURNAL OF GENERAL PHYSIOLOGY
(2021)
Article
Cell Biology
Erin F. Reinhart, Nicole A. Litt, Sarah Katzenell, Maria Pellegrini, Ai Yamamoto, Michael J. Ragusa
Summary: The FYVE domain of ALFY has weaker binding to PI(3)P-containing membranes compared to other FYVE domains due to a unique glutamic acid, affecting its targeting ability and protein aggregate clearance in vivo. This distinct membrane binding property of ALFY's FYVE domain has significant implications for its cellular function.
Article
Parasitology
Zhenyu Ren, Qiyang Shi, Simin Xu, Jiahui Xu, Yi Yin, Zhijie Lin, Sui Xu, Xiaoqin Ma, Yaobao Liu, Guoding Zhu, Xinlong He, Jingyuan Lu, Yinyue Li, Wenwen Zhang, Jiali Liu, Yun Yang, Eun-Taek Han, Jun Cao, Feng Lu
Summary: This study investigated the genetic variation, antigenicity, and immunogenicity of PocDBP-RII in Plasmodium ovale curtisi. The results showed that PocDBP-RII sequences were highly conserved in clinical isolates. The study also found that rPocDBP-RII protein could induce specific antibodies and immune response mediated by IFN-γ-producing CD4+ and CD8+ T cells, as well as memory T cells, suggesting its potential as a vaccine candidate.
PARASITES & VECTORS
(2023)
Article
Biochemistry & Molecular Biology
Claudia B. Zraly, Richard Schultz, Manuel O. Diaz, Andrew K. Dingwall
Summary: Enhancer activation by the MLR family of H3K4 mono-methyltransferases requires proper recognition of histones for the deposition of the mono-methyl mark. The PHD zinc finger domains of MLR proteins are responsible for recognizing specific histones and depositing the mono-methyl mark. The spacer between the first two PHD zinc finger domains is critical for optimal histone engagement.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Anil K. Pandey, Himal K. Ganguly, Sudipta Kumar Sinha, Kelly E. Daniels, Glenn P. A. Yap, Sandeep Patel, Neal J. Zondlo
Summary: Phosphorylation and dephosphorylation of proteins play a crucial role in cellular responses and function. The structural effects of serine and threonine phosphorylation have been studied and it was found that threonine exhibits a unique disorder-to-order transition upon phosphorylation. This research provides insights into the differential use and evolution of phosphorylation sites in proteins.
ACS CHEMICAL BIOLOGY
(2023)
Article
Virology
Jeremie Prevost, Jonathan Richard, Romain Gasser, Halima Medjahed, Frank Kirchhoff, Beatrice H. Hahn, John C. Kappes, Christina Ochsenbauer, Ralf Duerr, Andres Finzi
Summary: HIV-1 Nef and Vpu are important for viral immune evasion, release, and replication. A new method was developed to detect these accessory proteins and their cellular substrates simultaneously. The study found that Vpu cannot compensate for the lack of a functional Nef, which is significant for studying ADCC responses using Nef-defective viruses.
JOURNAL OF VIROLOGY
(2022)
Editorial Material
Biochemistry & Molecular Biology
Philippe Begin, Jeannie Callum, Richard Cook, Erin Jamula, Yang Liu, Andres Finzi, Donald M. Arnold
Correction
Biochemistry & Molecular Biology
Philippe Begin, Jeannie Callum, Erin Jamula, Richard Cook, Nancy M. Heddle, Alan Tinmouth, Michelle P. Zeller, Guillaume Beaudoin-Bussieres, Luiz Amorim, Renee Bazin, Kent Cadogan Loftsgard, Richard Carl, Michael Chasse, Melissa M. Cushing, Nick Daneman, Dana V. Devine, Jeannot Dumaresq, Dean A. Fergusson, Caroline Gabe, Marshall J. Glesby, Na Li, Yang Liu, Allison McGeer, Nancy Robitaille, Bruce S. Sachais, Damon C. Scales, Lisa Schwartz, Nadine Shehata, Alexis F. Turgeon, Heidi Wood, Ryan Zarychanski, Andres Finzi, Donald M. Arnold
Article
Virology
Shilei Ding, Damien Adam, Guillaume Beaudoin-Bussieres, Alexandra Tauzin, Shang Yu Gong, Romain Gasser, Annemarie Laumaea, Sai Priya Anand, Anik Prive, Catherine Bourassa, Halima Medjahed, Jeremie Prevost, Hugues Charest, Jonathan Richard, Emmanuelle Brochiero, Andres Finzi
Summary: Using the native full-length Spike protein expressed on the surface of infected cells in serological assays is effective in recapitulating findings and can be recognized by plasma from convalescent and vaccinated individuals.
Article
Cell Biology
Guillaume Beaudoin-Bussieres, Yaozong Chen, Irfan Ullah, Jeremie Prevost, William D. Tolbert, Kelly Symmes, Shilei Ding, Mehdi Benlarbi, Shang Yu Gong, Alexandra Tauzin, Romain Gasser, Debashree Chatterjee, Dani Vezina, Guillaume Goyette, Jonathan Richard, Fei Zhou, Leonidas Stamatatos, Andrew T. McGuire, Hughes Charest, Michel Roger, Edwin Pozharski, Priti Kumar, Walther Mothes, Pradeep D. Uchil, Marzena Pazgier, Andres Finzi
Summary: Emerging evidence suggests that both neutralizing and Fc-mediated effector functions of antibodies are important for protection against SARS-CoV-2. A non-neutralizing antibody, CV3-13, with potent Fc-mediated effector functions, was found to bind to a specific epitope of the SARS-CoV-2 spike from a unique angle. In mouse experiments, the Fc-enhanced version of CV3-13 delayed virus spread, neuroinvasion, and death, and the combination of Fc-enhanced CV3-13 with a neutralizing antibody completely protected mice from lethal SARS-CoV-2 infection.
Article
Cell Biology
Wenwe Li, Yaozong Chen, Jeemie Prevost, Irfan Ullah, Maoli Lu, Shang Yu Gong, Alexandra Tauzin, Romain Gasser, Dani Vezina, Sai Priya Anand, Guillaume Goyette, Debashree Chaterjee, Shilei Ding, William D. Tolbert, Michael W. Grunst, Yuxia Bo, Shijian Zhang, Jonathan Richard, Fei Zhou, Rick K. Huang, Lothar Esser, Allison Zeher, Marceline Cote, Priti Kumar, Joseph Sodroski, Di Xia, Pradeep D. Uchil, Marzena Pazgier, Andres Finzi, Walther Mothes
Summary: This study elucidates the structural basis and mode of action for two potent SARS-CoV-2 spike-neutralizing monoclonal antibodies. CV3-1 triggers shedding of the S1 subunit by binding to a loop structure in the receptor-binding domain (RBD), while CV3-25 inhibits membrane fusion by binding to an epitope in the stem helix region of the S2 subunit. Designing vaccine immunogens that incorporate conserved regions in the RBD and stem helix region could elicit pan-coronavirus protective immune responses.
Article
Immunology
William D. Tolbert, Dung N. Nguyen, Marina Tuyishime, Andrew R. Crowley, Yaozong Chen, Shalini Jha, Derrick Goodman, Valerie Bekker, Sarah V. Mudrak, Anthony L. DeVico, George K. Lewis, James F. Theis, Abraham Pinter, M. Anthony Moody, David Easterhoff, Kevin Wiehe, Justin Pollara, Kevin O. Saunders, Georgia D. Tomaras, Margaret Ackerman, Guido Ferrari, Marzena Pazgier
Summary: The successful rhesusization of human mAbs targeting HIV-1 envelope epitopes in Non-Human Primates (NHPs) demonstrates the preservation of antibody specificity and function. This methodology is not only relevant for HIV-1 vaccine trials, but also applicable to antibodies for various other purposes.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Medicine, Research & Experimental
Thomas J. Esparza, Yaozong Chen, Negin P. Martin, Helle Bielefeldt-Ohmann, Richard A. Bowen, William D. Tolbert, Marzena Pazgier, David L. Brody
Summary: NIH-CoVnb-112, a potent single-domain nanobody specific for the receptor-binding domain (RBD) of SARS-CoV-2, has been found to have broad in vitro neutralization capability against variant SARS-CoV-2 pseudoviruses. In an in vivo pilot study, nebulized delivery of NIH-CoVnb-112 effectively reduced weight loss, viral burden, and lung pathology in a Syrian hamster model of COVID-19. These findings support the further development of NIH-CoVnb-112 as a potential adjunct therapeutic for SARS-CoV-2 infection.
Article
Microbiology
Alexander F. Flynn, Rebekah T. Taylor, Marzena E. Pazgier, Sasisekhar Bennuru, Alyssa R. Lindrose, Spencer L. Sterling, C. Paul Morris, Brynna Gleeson, Tim K. Maugel, Thomas B. Nutman, Edward Mitre
Summary: Lymphatic filariasis is a global disease caused by parasitic nematodes that affect millions of people. Identifying new drug and vaccine targets in adult filariae could aid elimination efforts. Bma-LAD-2 was identified as an essential protein for adult Brugia malayi, making it a potential therapeutic target.
Article
Multidisciplinary Sciences
Yaozong Chen, Lulu Sun, Irfan Ullah, Guillaume Beaudoin-Bussieres, Sai Priya Anand, Andrew P. Hederman, William D. Tolbert, Rebekah Sherburn, Dung N. Nguyen, Lorie Marchitto, Shilei Ding, Di Wu, Yuhong Luo, Suneetha Gottumukkala, Sean Moran, Priti Kumar, Grzegorz Piszczek, Walther Mothes, Margaret E. Ackerman, Andres Finzi, Pradeep D. Uchil, Frank J. Gonzalez, Marzena Pazgier
Summary: Researchers developed a bivalent ACE2-Fc with enhanced recognition of SARS-CoV-2 and improved antibody effector functions. In mouse models, this ACE2-Fc delayed death and effectively treated lethal SARS-CoV-2 infection through neutralization and effector functions.
Article
Cell Biology
Annemarie Laumaea, Lorie Marchitto, Shilei Ding, Guillaume Beaudoin-Bussieres, Jeremie Prevost, Romain Gasser, Debashree Chatterjee, Gabrielle Gendron-Lepage, Halima Medjahed, Hung-Ching Chen, Amos B. Smith III, Haitao Ding, John C. Kappes, Beatrice H. Hahn, Frank Kirchhoff, Jonathan Richard, Ralf Duerr, Andres Finzi
Summary: The conformation of HIV-1 envelope (Env) determines the susceptibility of infected CD4(+) T cells to antibody-dependent cellular cytotoxicity (ADCC). The downregulation of CD4 on infected macrophages by Nef, Vpu, and Env has a lesser impact on Env conformation and ADCC sensitivity compared to CD4(+) T cells. However, treatment of infected macrophages with small CD4 mimetics exposes vulnerable CD4-induced Env epitopes and sensitizes them to ADCC.
Editorial Material
Microbiology
Jeremie Prevost, Bryce M. Warner, David Safronetz
NATURE MICROBIOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Beatriz Pacheco, Alberto Fernandez-Oliva, Moises Garcia-Serradilla, Cristina Risco
Summary: In this study, the antiviral capacity of four repurposed drugs against BUNV infection was tested. Digoxin showed the strongest inhibitory effect on BUNV infection in Vero and HEK293T cells, as it reduced viral protein expression, affected the cell cycle, and altered mitochondrial morphology. The inhibition of the Na+/K+ ATPase by digoxin played a key role in its antiviral activity.
JOURNAL OF GENERAL VIROLOGY
(2023)
Article
Multidisciplinary Sciences
Jeremie Prevost, Yaozong Chen, Fei Zhou, William D. Tolbert, Romain Gasser, Halima Medjahed, Manon Nayrac, Dung N. Nguyen, Suneetha Gottumukkala, Ann J. Hessell, Venigalla B. Rao, Edwin Pozharski, Rick K. Huang, Doreen Matthies, Andres Finzi, Marzena Pazgier
Summary: Resistance to the HIV-1 entry inhibitor temsavir is not solely determined by residue 375, but also involves other residues within the gp120 inner domain layers. The resistance is mediated by crosstalk between residue 375 and the inner domain layers. Additionally, temsavir has the ability to adjust its binding mode to accommodate changes in Env conformation, contributing to its broad antiviral activity.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Jonathan Richard, Jeremie Prevost, Catherine Bourassa, Nathalie Brassard, Marianne Boutin, Mehdi Benlarbi, Guillaume Goyette, Halima Medjahed, Gabrielle Gendron-Lepage, Fleur Gaudette, Hung-Ching Chen, William D. Tolbert, Amos B. Smith, Marzena Pazgier, Mathieu Dube, Andrew Clark, Walther Mothes, Daniel E. Kaufmann, Andres Finzi
Summary: While HIV-1-mediated CD4 downregulation protects infected cells from ADCC, shed gp120 binds to uninfected bystander CD4+ T cells, sensitizing them to ADCC mediated by HIV+ plasma and triggering a cytokine burst. Temsavir, an HIV-1 attachment inhibitor, not only prevents gp120-CD4 interaction and alters Env antigenicity, but also blocks the immunomodulatory activities of shed gp120. Temsavir protects uninfected bystander CD4+ cells from ADCC responses and cytokine burst by preventing gp120 interaction, reducing shedding, and altering antigenicity.
CELL CHEMICAL BIOLOGY
(2023)