Article
Multidisciplinary Sciences
Lijing Su, Muhammad Athamna, Ying Wang, Junmei Wang, Marina Freudenberg, Tao Yue, Jianhui Wang, Eva Marie Y. Moresco, Haoming He, Tsaffrir Zor, Bruce Beutler
Summary: Sulfatides can activate mouse immune responses via the TLR4-MD-2 complex, but exhibit antagonistic effects in human cells. Their activity is related to the presence of the sulfate group and the length of the fatty acid chain, and their structure mimics the activation mechanism of molecules like LPS in receptors.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Julien Orlans, Carole Vincent-Monegat, Isabelle Rahioui, Catherine Sivignon, Agata Butryn, Laurent Soulere, Anna Zaidman-Remy, Allen M. Orville, Abdelaziz Heddi, Pierre Aller, Pedro Da Silva
Summary: The study analyzed the activity of different isoforms of Drosophila PGRP-LB towards various PGN substrates and elucidated the mechanism of amidase activity through site directed mutagenesis and X-ray structure determination. The findings suggest a dynamic role of residue Y78 in the amidase mechanism by nucleophilic attack through a water molecule to the carbonyl group of the amide function destabilized by Zn2+.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Jiali Yang, Takahiro Mori, Xingxing Wei, Yudai Matsuda, Ikuro Abe
Summary: The novel isomerase NsrQ from Aspergillus novofumigatus plays a key role in the biosynthesis of fungal tetrahydroxanthones by catalyzing a two-step isomerization reaction. Through biochemical and structural characterizations, it was found that NsrQ and its homologue Dcr3 utilize Glu and His residues as acid-base catalysts and important hydrophobic residues for shaping the active site pocket for substrate binding. The crystal structures of NsrQ and Dcr3 revealed their cone-shaped alpha + beta barrel fold and similarities to the nuclear transport factor 2-like superfamily enzymes.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Biochemistry & Molecular Biology
Christo N. Nanev, Emmanuel Saridakis, Naomi E. Chayen
Summary: X-ray crystallography is currently the dominant method for determining the structure of proteins and biomolecules. However, it faces challenges in obtaining high-resolution data from small protein crystals. Serial crystallography using XFELs is a promising alternative method that can produce excellent structural data from weakly diffracting objects. In this study, the authors calculate the mean crystal size and growth time needed for batch crystallization, which is the main method for preparing microcrystalline slurries. They also consider the impact of impurities on the growth of microcrystals. Experimental results with lysozyme support the theoretical predictions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Lorenzo Soini, Seppe Leysen, Jeremy Davis, Marta Westwood, Christian Ottmann
Summary: SLP76 is an important adaptor protein that interacts with 14-3-3 proteins to control TCR signaling through phosphorylation on Ser376. By determining the crystal structure and characterizing the binding properties, researchers have laid the foundation for drug design efforts targeting the 14-3-3/SLP76 interaction.
Article
Biochemistry & Molecular Biology
Yan-Hua Li, Hai-Feng Hou, Zhi Geng, Heng Zhang, Zhun She, Yu-Hui Dong
Summary: This study presents the crystal structure of the multi-functional enzyme PBCV1dCD in complex with different nucleotide substrates. The results reveal that PBCV1dCD can deaminate not only dCMP and dCTP, but also dCDP, making it unique among other dCD family proteins. The analysis of the structural basis identifies a key residue, Trp121, which is essential for the deamination and substrate binding ability of PBCV1dCD.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2022)
Article
Biochemistry & Molecular Biology
Lucile Senicourt, Albane le Maire, Frederic Allemand, JoAo E. Carvalho, Laura Guee, Pierre Germain, Michael Schubert, Pau Bernado, William Bourguet, Nathalie Sibille
Summary: Retinoic acid receptors (RARs) and retinoid X receptors (RXRs) form heterodimers to activate target gene transcription by recruiting co-activator complexes. The nuclear receptor co-activator TIF2 interacts with the ligand-binding domain of NRs to mediate recruitment, showing a largely disordered protein with partially structured regions, including the NR-boxes and their evolutionary conserved flanking regions. NMR and X-ray crystallographic data reveal a multisite binding of the NR-boxes and an active role of their flanking regions in the interaction.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Review
Pharmacology & Pharmacy
Hadiatullah Hadiatullah, Zhao He, Zhiguang Yuchi
Summary: This review summarizes recent advances in the study of high-resolution structures of ryanodine receptors (RyRs) and discusses the gating mechanisms, regulatory mechanisms, and the impact of disease-causing mutations on the structure and function of RyRs. The structural information obtained could contribute to the diagnosis and development of pharmacological therapies for related diseases.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Men Thi Hoai Duong, Hee-Chul Ahn
Summary: This study utilized virtual fragment screening, STD NMR, in vitro kinase assay, and X-ray crystallography to identify 27 initial hits targeting JNK3 and demonstrating activity inhibition. The structures of JNK3 with a fragment and a potent inhibitor were determined by X-ray crystallography, revealing a common JNK3-binding feature.
Article
Biochemistry & Molecular Biology
Stavros Azinas, Marta Carroni
Summary: Cryo-EM is a major tool for determining protein structures, while AlphaFold2 enables high-confidence atomic models for polypeptide chains. Cryo-EM retains unique characteristics for determining structures of macromolecular complexes, allowing for near-atomic structures and exploring conformational panoramas. It also has the potential to develop a structural proteomic approach using ex vivo specimens.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2023)
Review
Pharmacology & Pharmacy
Claudia Grossmann, Brian Almeida-Prieto, Alexander Nolze, Diego Alvarez de la Rosa
Summary: The mineralocorticoid receptor (MR) has evolved into a key player in maintaining volume and electrolyte homeostasis, as well as in pathological changes in various tissues. However, there is still a lack of understanding about the unique features and mechanisms specific to MR.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Review
Pharmacology & Pharmacy
Adam C. Oken, Ipsita Krishnamurthy, Jonathan C. Savage, Nicolas E. Lisi, Michael H. Godsey, Steven E. Mansoor
Summary: Extracellular ATP is a critical signaling molecule with a wide range of concentrations. P2X receptors (P2XRs) sense extracellular ATP and are involved in various physiological and pathological processes. Structural biology can aid in the development of potential therapeutic ligands for P2XRs.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Kyung Yeol Ko, Wan Seok Song, Jeongho Park, Geun-Shik Lee, Sung-Il Yoon
Summary: Toll-like receptor 15 (TLR15) is a unique immune receptor in birds and reptiles that activates innate immunity in response to pathogen-associated molecular patterns (PAMPs), and its TIR domain has structural differences from other TLRs, resulting in a unique dimeric structure. Comparative analysis of TIR structures and sequences provides insights into the interaction between TLR15(TIR) and a signaling adaptor protein.
Article
Biochemistry & Molecular Biology
Michal Mayer, Yulia Matiuhin, Mickal Nawatha, Orly Tabachnikov, Inbar Fish, Nili Schutz, Hay Dvir, Meytal Landau
Summary: The bacterial tyrosine kinase BceF from Burkholderia cepacia is structurally characterized in this study and found to have unique variations compared to other BY-kinases, offering a potential for development of specific inhibitors targeting Burkholderia cepacia virulence.
Article
Biochemistry & Molecular Biology
Danny Farhat, Fatemeh Rezaei, Milica Ristovski, Yidai Yang, Albert Stancescu, Lucia Dzimkova, Sabrina Samnani, Jean-Francois Couture, Jyh-Yeuan Lee
Summary: The ATP-binding cassette (ABC) sterol transporters play important roles in maintaining cholesterol homeostasis and preventing abnormal accumulation of plant sterols. The crystal structure analysis of ABCG5/G8 suggests a sterol-binding site and reveals its functional implications in cholesterol/sterol transport. Furthermore, docking analysis reveals the sterol-binding selectivity of ABCG5/G8, providing insights into its physiological role.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Microbiology
Callum Talbot-Cooper, Teodors Pantelejevs, John P. Shannon, Christian R. Cherry, Marcus T. Au, Marko Hyvonen, Heather D. Hickman, Geoffrey L. Smith
Summary: This study reports that the poxvirus protein 018 inhibits interferon-induced signaling by binding to the SH2 domain of STAT1. The crystal structure of the 018:STAT1 complex reveals a phosphotyrosine-independent mode of 018 binding to STAT1, and the STAT1-binding motif of 018 shows similarity to STAT1-binding proteins from Nipah virus.
CELL HOST & MICROBE
(2022)
Article
Biotechnology & Applied Microbiology
William N. D. Gao, Chen Gao, Janet E. Deane, David C. J. Carpentier, Geoffrey L. Smith, Stephen C. Graham
Summary: Researchers have solved the crystal structure of the vaccinia virus E2 protein, revealing its unique folded domains. Recent advances in deep learning methods have greatly improved the accuracy of predicting protein structures, which has significant implications for structural virology and molecular virology.
JOURNAL OF GENERAL VIROLOGY
(2022)
Article
Immunology
Yanchun Peng, Suet Ling Felce, Danning Dong, Frank Penkava, Alexander J. Mentzer, Xuan Yao, Guihai Liu, Zixi Yin, Ji-Li Chen, Yongxu Lu, Dannielle Wellington, Peter A. C. Wing, Delaney C. C. Dominey-Foy, Chen Jin, Wenbo Wang, Megat Abd Hamid, Ricardo A. Fernandes, Beibei Wang, Anastasia Fries, Xiaodong Zhuang, Neil Ashley, Timothy Rostron, Craig Waugh, Paul Sopp, Philip Hublitz, Ryan Beveridge, Tiong Kit Tan, Christina Dold, Andrew J. Kwok, Charlotte Rich-Griffin, Wanwisa Dejnirattisa, Chang Liu, Prathiba Kurupati, Isar Nassiri, Robert A. Watson, Orion Tong, Chelsea A. Taylor, Piyush Kumar Sharma, Bo Sun, Fabiola Curion, Santiago Revale, Lucy C. Garner, Kathrin Jansen, Ricardo C. Ferreira, Moustafa Attar, Jeremy W. Fry, Rebecca A. Russell, Hans J. Stauss, William James, Alain Townsend, Ling-Pei Ho, Paul Klenerman, Juthathip Mongkolsapaya, Gavin R. Screaton, Calliope Dendrou, Stephen N. Sansom, Rachael Bashford-Rogers, Benny Chain, Geoffrey L. Smith, Jane A. McKeating, Benjamin P. Fairfax, Paul Bowness, Andrew J. McMichael, Graham Ogg, Julian C. Knight, Tao Dong
Summary: Specific CD8(+) T cell responses targeting NP105-113-B*07:02 are associated with mild COVID-19 disease and high antiviral efficacy, providing potential targets for T cell vaccine design. These T cell responses show long-lasting preservation of antiviral functionality post-infection.
Article
Biochemistry & Molecular Biology
Hannah T. Baddock, Sanja Brolih, Yuliana Yosaatmadja, Malitha Ratnaweera, Marcin Bielinski, Lonnie P. Swift, Abimael Cruz-Migoni, Haitian Fan, Jeremy R. Keown, Alexander P. Walker, Garrett M. Morris, Jonathan M. Grimes, Ervin Fodor, Christopher J. Schofield, Opher Gileadi, Peter J. McHugh
Summary: The nsp14-nsp10 complex of SARS-CoV-2 has been found to possess RNase activity and is capable of digesting various RNA structures. Its activity is enhanced by the viral RNA-dependent RNA polymerase complex nsp12-7-8. Inhibitors of nsp14-nsp10, including ebselen and raltegravir, have been identified and may have potential use in the treatment of COVID-19.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Virology
Mitchell A. Pallett, Yongxu Lu, Geoffrey L. Smith
Summary: The transcription factors IRF3 and NF-kappa B play crucial roles in the immune response to viral and bacterial pathogens. This study identifies DDX50 as a factor that promotes the activation of the IRF3 signaling pathway in response to viral RNA or infection with RNA and DNA viruses. Deletion of DDX50 impairs IRF3 phosphorylation and the expression of genes and cytokines involved in the immune response. Loss of DDX50 also leads to increased replication and dissemination of various viruses. The findings highlight the important role of DDX50 as a broad-ranging viral restriction factor.
Article
Microbiology
Alice A. Torres, Stephanie L. Macilwee, Amir Rashid, Sarah E. Cox, Jonas D. Albarnaz, Claudio A. Bonjardim, Geoffrey L. Smith
Summary: This paragraph mainly introduces the multiple functions of the Spir-1 protein, including enhancing immune response and inhibiting virus infection. The study also found that the viral protein K7 can directly bind to Spir-1 and enhance the virulence of the virus.
Article
Microbiology
Kamal L. Nahas, Viv Connor, Katharina M. Scherer, Clemens F. Kaminski, Maria Harkiolaki, Colin M. Crump, Stephen C. Graham
Summary: Herpes simplex virus-1 (HSV-1) infection causes morphological changes in cellular compartments, as well as specific organelles. These changes can be captured using soft X-ray tomography, which reveals the significant impact of HSV-1 infection on the morphology of cellular compartments.
Article
Biochemistry & Molecular Biology
Tomasz H. Benedyk, Viv Connor, Eve R. Caroe, Maria Shamin, Dmitri I. Svergun, Janet E. Deane, Cy M. Jeffries, Colin M. Crump, Stephen C. Graham
Summary: Herpes simplex virus-1 (HSV-1) alters cellular membrane lipid composition during infection. This study demonstrates that a virus-encoded protein, pUL21, promotes the conversion of ceramide (Cer) to sphingomyelin (SM) by activating CERT. The study also reveals the importance of specific protein-protein interactions in HSV-1 mediated sphingolipid metabolism.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biology
Iain M. Hay, Katie E. Mulholland, Tiffany Lai, Stephen C. Graham, Hayley J. Sharpe, Janet E. Deane
Summary: The research demonstrates that PTPRK selectively dephosphorylates substrates by binding to Afadin, indicating that PTP substrate specificity can be determined by protein-protein interactions. This phosphorylation-independent interaction, mediated through binding to a non-catalytic domain, highlights the potential function of receptor PTPs as intracellular scaffolds.
Article
Biochemistry & Molecular Biology
Iain M. Hay, Maria Shamin, Eve R. Caroe, Ahmed S. A. Mohanned, Dmitri I. Svergun, Cy M. Jeffries, Stephen C. Graham, Hayley J. Sharpe, Janet E. Deane
Summary: Type IIB receptor protein tyrosine phosphatases mediate cell adhesion and signaling through their extracellular and cytoplasmic domains, respectively. The crystal structure of PTPRK has revealed an intermembrane adhesion mode consistent with other family members. Comparison with PTPRM structure suggests that conformational differences between the domains may contribute to homophilic specificity. Analysis of the full-length PTPRM and PTPRK proteins using small-angle X-ray scattering reveals rigid extended conformations and one residue difference at the interaction interface that affects dimer formation.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Virology
Natalia S. S. Barbosa, Juan O. O. Concha, Luis L. P. daSilva, Colin M. M. Crump, Stephen C. C. Graham
Summary: Oropouche virus causes a debilitating illness called Oropouche fever, which is common in South America. The virus has the ability to reassort its genome and has caused multiple epidemics in the region over the last 50 years, posing a significant threat to public health. The study investigates the cellular determinants and mechanisms involved in Oropouche virus replication and secretion.
JOURNAL OF VIROLOGY
(2023)
Article
Biochemical Research Methods
Jack D. Whitehead, Jonathan M. Grimes, Jeremy R. Keown
Summary: Bornaviruses are RNA viruses that infect a wide range of hosts including mammals, reptiles, and birds. This study presents the structure of the oligomerization domain of the phosphoprotein, which is an important component of the bornavirus replication complex. The findings provide valuable insights into the assembly process of the phosphoprotein and its role in viral replication.
ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY COMMUNICATIONS
(2023)
Article
Immunology
Delphine J. Depierreux, Geoffrey L. Smith, Brian J. Ferguson
Summary: This study investigated the response of natural killer (NK) cells to vaccinia virus (VACV) infection. The results showed broad changes in NK cell transcriptional activity, indicating recognition of infected cells and exposure to cytokines. Specific NK surface receptors were also altered, and memory-associated NK markers were upregulated. However, adoptive transfer of VACV-experienced NK populations did not provide protection. Comparison with the NK cell response to murine cytomegalovirus (MCMV) infection revealed both common features and distinct transcriptional programs initiated by VACV. The study also found overlap between the NK transcriptional response in humans vaccinated with modified vaccinia Ankara (MVA), suggesting conservation between different host species. These findings provide new insights into NK cell activation, function, and homeostasis during VACV infection and have implications for VACV-based therapeutics.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Hazel Stewart, Yongxu Lu, Sarah O'Keefe, Anusha Valpadashi, Luis Daniel Cruz-Zaragoza, Hendrik A. Michel, Samantha K. Nguyen, George W. Carnell, Nina Lukhovitskaya, Rachel Milligan, Yasmin Adewusi, Irwin Jungreis, Valeria Lulla, David A. Matthews, Stephen High, Peter Rehling, Edward Emmott, Jonathan L. Heeney, Andrew D. Davidson, James R. Edgar, Geoffrey L. Smith, Andrew E. Firth
Summary: The SARS-CoV-2 genome encodes multiple accessory proteins, including a previously uncharacterized ORF3c protein. ORF3c localizes to mitochondria and inhibits innate immunity by restricting IFN-beta production. It has inhibitory effects after stimulation with cytoplasmic RNA helicases RIG-I or MDA5 or adaptor protein MAVS, but not under other stimulation conditions.
