Article
Biochemical Research Methods
Cristian D. Loaiza, Naveen Duhan, Matthew Lister, Rakesh Kaundal
Summary: This study developed the genome-scale host-pathogen protein interaction networks between human and B. pseudomallei, identifying potential novel virulence factors and their interacting partners. The findings offer new insights for studying infection mechanisms and developing prevention measures.
BRIEFINGS IN BIOINFORMATICS
(2021)
Article
Biology
George W. Mobbs, Adli A. Aziz, Samuel R. Dix, G. M. Blackburn, Sveta E. Sedelnikova, Thomas C. Minshull, Mark J. Dickman, Patrick J. Baker, Sheila Nathan, Mohd Firdaus Raih, David W. Rice
Summary: Burkholderiapseudomallei lethal factor 1 (BLF1) inhibits mammalian protein synthesis by deamidating eukaryotic RNA helicase, eIF4A. The complex structure of BLF1 and human eIF4A reveals the interaction between the two proteins in the RecA-like domains, which show a unique conformation compared to other eIF4A structures and may be associated with RNA binding. Comparison with other deamidases and cysteine proteases suggests a convergent evolution of their Cys-His active sites. The crystal structure of this toxin and its target provides insights into substrate specificity and aids in the development of inhibitors for melioidosis treatment.
COMMUNICATIONS BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Denis V. Petrovskiy, Kirill S. Nikolsky, Vladimir R. Rudnev, Liudmila I. Kulikova, Tatiana V. Butkova, Kristina A. Malsagova, Arthur T. Kopylov, Anna L. Kaysheva
Summary: This article introduces a new tool called SAFoldNet, which uses neural networks to search and align protein structures. The study shows that this method is competitive in searching and aligning protein structures, and a user-friendly web interface service has been developed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Microbiology
Ahmad-Kamal Ghazali, Mohd Firdaus-Raih, Asqwin Uthaya Kumar, Wei-Kang Lee, Chee-Choong Hoh, Sheila Nathan
Summary: This study investigated the transcriptome-level adaptations of B. pseudomallei when growing in soil and during infection. The results showed that the bacterium induced the expression of metabolism and transporter proteins in soil, while virulence factors, metabolism, and bacterial defense mechanisms were upregulated during infection. Additionally, the capsular polysaccharide and quorum-sensing pathways were inhibited during infection. These findings provide crucial insights into the adaptation mechanisms of B. pseudomallei in soil and during infection.
MICROBIOLOGY SPECTRUM
(2023)
Article
Immunology
Yee-Chin Wong, Raeece Naeem, Moataz Abd El Ghany, Chee-Choong Hoh, Arnab Pain, Sheila Nathan
Summary: This study identified essential genes of B. pseudomallei and genes required for growth under nutrient-depleted conditions using TraDIS. The study also identified genes associated with B. pseudomallei survival and adaptation in the C. elegans intestinal lumen using a C. elegans infection model.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Anna Di Fiore, Viviana De Luca, Emma Langella, Alessio Nocentini, Martina Buonanno, Simona Maria Monti, Claudiu T. Supuran, Clemente Capasso, Giuseppina De Simone
Summary: This paper presents a detailed characterization of BpsyCA, a y-carbonic anhydrase from Burkholderia pseudomallei, highlighting its catalytic activity, crystal structure, and the role of residues in its catalytic mechanism and ligand recognition. These findings provide an important starting point for the development of new anti-melioidosis drugs targeting BpsyCA.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Neil Lorente Cobo, Stephanie Sibinelli-Sousa, Jacob Biboy, Waldemar Vollmer, Ethel Bayer-Santos, Gerd Prehna
Summary: This study reveals the structure and function of the T6SS effector Tlde1a from Salmonella Typhimurium. Tlde1a possesses a unique LD-transpeptidase fold, which is structurally altered to create its toxic effect and plays an important role in bacterial competition.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Gastroenterology & Hepatology
Javier Sanchez-Villamil, Daniel Tapia, Nittaya Khakhum, Steven G. Widen, Alfredo G. Torres
Summary: This study highlights the importance of the type 6 secretion system (T6SS) in the gastrointestinal pathogenesis of Burkholderia pseudomallei (Bpm), demonstrating that T6SS is essential for full virulence of Bpm during intestinal infection. RNA-seq analysis on Bpm-infected intestinal epithelial cells revealed dysregulation in TNF-alpha signaling via NF-kappa B pathway in absence of T6SS, impacting inflammatory processes and cell death. Bacterial transcriptome analysis identified virulence factors and regulatory proteins associated with T6SS.
Article
Biochemistry & Molecular Biology
Ezekiel Ze Ken Cheong, Jun Ping Quek, Liu Xin, Chaoqiang Li, Jing Yi Chan, Chong Wai Liew, Yuguang Mu, Jie Zheng, Dahai Luo
Summary: This study reports a novel crystal structure of RubPro and investigates its functions. It was found that RubPro has protease and deubiquitylation activities, potentially modulating the host's immune responses. These structural and functional insights advance our understanding of RUBV replication and may facilitate the development of antiviral therapeutics.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Jing Guo, Oriana S. Fisher
Summary: A large number of copper binding proteins use the cupredoxin domain to coordinate metal ions. This domain is common in a diverse group of copper binding domains. The cupredoxin fold is ideal for various purposes such as electron transfer and enzyme catalysis. The core structure remains stable upon metal binding, but variations within the coordination environment of the metal site result in different copper binding affinities and spectroscopic properties.
JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Alexis Huet, Bonnie Oh, Josh Maurer, Robert L. Duda, James F. Conway
Summary: Tailed bacteriophages and herpesviruses use a scaffold to assemble icosahedral capsids, with hexameric capsomers on the faces and pentameric capsomers at most vertices. The portal vertex structure of bacteriophage HK97 procapsid was determined, revealing a scaffold formed by the major capsid protein. The scaffold is organized into rigid helix-turn-strand structures on the capsomers and trimeric coiled-coil towers around the portal, explaining the coordination of assembly at this early step.
Article
Biochemistry & Molecular Biology
Dan Yu, Gundeep Kaur, Robert M. Blumenthal, Xing Zhang, Xiaodong Cheng
Summary: The study reveals significant differences in catalytic efficiency and substrate binding affinities among different human RNA methyltransferases, as well as their preferences for pH and ionic strength. It highlights the diversity of enzymatic mechanisms and substrate specificities of RNA adenosine methyltransferases, underscoring the importance of assay optimization in their study.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biology
Frederic Angles, Chao Wang, William E. Balch
Summary: Spatial covariance analysis shows how each residue in the critical fold region of chloride channel CFTR, defective in cystic fibrosis patients, contributes to CFTR's export from the endoplasmic reticulum and function in the cell.
COMMUNICATIONS BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Naifu Zhang, Keith J. Olsen, Darby Ball, Sean J. Johnson, Sheena D'Arcy
Summary: Using various techniques, this study characterized the interaction between Mtr4 and different RNAs. The results revealed consistent interactions between the helicase core of Mtr4 and various RNAs, as well as novel interactions between a region of the arch domain and RNA. These interactions play a crucial role in RNA unwinding and modulate Mtr4's discrimination between different RNAs.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Multidisciplinary Sciences
Rahil Taujale, Zhongliang Zhou, Wayland Yeung, Kelley W. Moremen, Sheng Li, Natarajan Kannan
Summary: The study utilizes interpretable deep learning to predict the folds of glycosyltransferases (GTs) without the need for sequence alignment, enabling the prediction of GTs with new folds.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Andrea Saponaro, Daniel Bauer, M. Hunter Giese, Paolo Swuec, Alessandro Porro, Federica Gasparri, Atiyeh Sadat Sharifzadeh, Antonio Chaves-Sanjuan, Laura Alberio, Giacomo Parisi, Gabriele Cerutti, Oliver B. Clarke, Kay Hamacher, Henry M. Colecraft, Filippo Mancia, Wayne A. Hendrickson, Steven A. Siegelbaum, Dario DiFrancesco, Martino Bolognesi, Gerhard Thiel, Bina Santoro, Anna Moroni
Summary: The HCN1-4 channel family is crucial for controlling automaticity in cardiac and neuronal pacemaker cells by regulating the hyperpolarization-activated cation current I-f/I-h. Cryo-EM structures of HCN4 with or without bound cAMP show insights into ligand-induced transitions, while analysis of open/closed pore states reveals mechanisms of channel gating and ion permeation. These findings contribute to understanding HCN channel gating, cyclic nucleotide-dependent modulation, and ion permeation mechanisms.
Article
Immunology
Flavio Di Pisa, Stefano De Benedetti, Enrico Mario Alessandro Fassi, Mauro Bombaci, Renata Grifantini, Angelo Musico, Roberto Frigerio, Angela Pontillo, Cinzia Rigo, Sandra Abelli, Romualdo Grande, Nadia Zanchetta, Davide Mileto, Alessandro Mancon, Alberto Rizzo, Alessandro Gori, Marina Cretich, Giorgio Colombo, Martino Bolognesi, Louise Jane Gourlay
Summary: Chagas disease is a vector-borne parasitic disease caused by the protozoan parasite Trypanosoma cruzi. It is affecting millions of people worldwide and is emerging in non-endemic regions due to climate change and increased immigration. This study focuses on developing new serodiagnostic molecules for early screening of the disease. A recombinant surface membrane antigen from T. cruzi was produced and its ability to detect plasma antibodies from infected patients was confirmed. The crystal structure of the antigen was also determined to guide the design of epitopes for CD diagnosis.
Review
Biochemistry & Molecular Biology
Marco Nardini, Alessandra Pesce, Martino Bolognesi
Summary: Truncated hemoglobins (trHbs) are a subclass of the globin family found in various organisms, including human pathogens. They have specific structural features and support different functions, such as detoxification, respiration, and oxygen sensing/storage.
MOLECULAR ASPECTS OF MEDICINE
(2022)
Article
Virology
Rafaela Milan Bonotto, Francesco Boni, Mario Milani, Antonio Chaves-Sanjuan, Silvia Franze, Francesca Selmin, Tommaso Felicetti, Martino Bolognesi, Soultana Konstantinidou, Monica Poggianella, Chantal L. Marquez, Federica Dattola, Monica Zoppe, Giuseppe Manfroni, Eloise Mastrangelo, Alessandro Marcello
Summary: Pyridobenzothiazolone derivatives are a promising class of antiviral compounds with broad-spectrum activity. The HeE1-17Y derivative has been shown to be potent against flaviviruses and West Nile virus. It interacts directly with viral particles, compromising their infectivity. This compound alters the viral membrane and exhibits virucidal activity.
Article
Biochemistry & Molecular Biology
Andrea Berardi, Oronza A. Botrugno, Giacomo Quilici, Jose Manuel Garcia Manteiga, Angela Bachi, Giovanni Tonon, Giovanna Musco
Summary: NSD1, NSD2, and NSD3 proteins belong to a family of histone 3 lysine 36 (H3K36) methyltransferases with similar domain architecture. However, their activities differ due to variations in their non-enzymatic domains and their ability to recognize different epigenetic marks and interactors. In this study, the researchers provide structural evidence for the distinctiveness of the PHDvC5HCH domain of NSD1 in recognizing the C2HR Zinc finger domain of Nizp1. They also demonstrate the functional association between Nizp1 and NSD1 in driving the unscheduled expression of certain genes in leukemia. These findings shed light on the pathophysiological relevance of the Nizp1-NSD1 interaction and suggest it as a potential therapeutic target for inhibiting oncogenic properties.
Article
Biotechnology & Applied Microbiology
Ferdinando M. Milazzo, Antonio Chaves-Sanjuan, Olga Minenkova, Daniela Santapaola, Anna M. Anastasi, Gianfranco Battistuzzi, Caterina Chiapparino, Antonio Rosi, Emilio Merlo Pich, Claudio Albertoni, Emanuele Marra, Laura Luberto, Cecile Viollet, Luigi G. Spagnoli, Anna Riccio, Antonio Rossi, Gabriella Santoro, Federico Ballabio, Cristina Paissoni, Carlo Camilloni, Martino Bolognesi, Rita De Santis
Summary: A human single-chain antibody called scFv76 can neutralize different variants of SARS-CoV-2 and demonstrate therapeutic efficacy in a mouse model of COVID-19, reducing lung inflammation and endothelial damage.
Article
Multidisciplinary Sciences
Tim Schulte, Antonio Chaves-Sanjuan, Giulia Mazzini, Valentina Speranzini, Francesca Lavatelli, Filippo Ferri, Carlo Palizzotto, Maria Mazza, Paolo Milani, Mario Nuvolone, Anne-Cathrine Vogt, Giovanni Palladini, Giampaolo Merlini, Martino Bolognesi, Silvia Ferro, Eric Zini, Stefano Ricagno
Summary: AA amyloidosis is a systemic disease characterized by the deposition of misfolded serum amyloid A protein (SAA) in multiple organs. The cryo-EM structure of AA amyloid from a cat with renal failure reveals a feline-specific sequence insert in the fibril core, which is highly similar to AA amyloid from cheetah with reported prion-like transmission.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Javier Garcia-Pardo, Andrea Bartolome-Nafria, Antonio Chaves-Sanjuan, Marcos Gil-Garcia, Cristina Visentin, Martino Bolognesi, Stefano Ricagno, Salvador Ventura
Summary: The study reports the cryo-electron microscopy structure of hnRNPDL-2 fibrils, revealing its stable, non-toxic, and nucleic acid-binding properties. The structure provides insights into the mechanism of hnRNPDL-2 fibrillation and its association with LGMD D3. Additionally, the study highlights how alternative splicing controls the assembly of different hnRNPDL isoforms, generating functional diversity.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Ida Freda, Cecile Exertier, Anna Barile, Antonio Chaves-Sanjuan, Mirella Vivoli Vega, Michail N. Isupov, Nicholas J. Harmer, Elena Gugole, Paolo Swuec, Martino Bolognesi, Anita Scipioni, Carmelinda Savino, Martino Luigi Di Salvo, Roberto Contestabile, Beatrice Vallone, Angela Tramonti, Linda Celeste Montemiglio
Summary: Specificity in protein-DNA recognition is determined by the structural and chemical features of the targeted DNA molecule. Using cryo-EM and crystallography, we elucidated the interactions driving the DNA recognition and binding by PdxR, a bacterial transcription factor. Our findings revealed the importance of electrostatic interactions and DNA bending in the allosteric regulation of DNA binding by PdxR. This study provides detailed insights into the structure and dynamics of the PdxR-DNA complex and the regulatory mechanisms of the MocR family of transcription factors.
NUCLEIC ACIDS RESEARCH
(2023)
Meeting Abstract
Biophysics
Andrea Saponaro, Daniel Bauer, Hunter Giese, Paolo Swuec, Alessandro Porro, Federica Gasparri, Atiyeh Sadat Sharifzadeh, Antonio Chaves-Sanjuan, Ermanno Uboldi, Anastasia Polyakova, Martino Bolognesi, Gerhard Thiel, Bina Santoro, Anna Moroni
EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS
(2021)
Meeting Abstract
Biochemistry & Molecular Biology
A. Chaves Sanjuan, A. Saponaro, D. Bauer, H. Giese, P. Swuec, A. Porro, F. Gasparri, A. Sharifzadeh, L. Alberio, O. Clarke, F. Mancia, W. Hendrickson, S. Siegelbaum, D. Dario, M. Bolognesi, G. Thiel, B. Santoro, A. Moroni
