Article
Virology
Xiaorong Meng, Michael Veit
Summary: This study found that the palmitoylation of HA of influenza B virus occurs in the ER, whereas acylation of HA of influenza A virus occurs in the Golgi. The ER-localized DHHCs 1, 2, 4, and 6 are responsible for acylation of HA of influenza B virus, which is different from the enzymes identified for acylation of HA of influenza A virus. The transmembrane region may be critical for the acylation of HA of influenza A and B viruses by different DHHCs.
JOURNAL OF VIROLOGY
(2023)
Article
Virology
Wang Xu, Yuhang Wang, Letian Li, Xiaoyun Qu, Quan Liu, Tiyuan Li, Shipin Wu, Ming Liao, Ningyi Jin, Shouwen Du, Chang Li
Summary: This study reveals a direct interaction between IFITM3 and influenza HA protein via the transmembrane domain, shedding light on the biological significance of IFITM3 in restricting influenza virus infection or HA-mediated antagonism or escape.
Article
Cell Biology
Jeroen Guns, Sam Vanherle, Jerome J. A. Hendriks, Jeroen F. J. Bogie
Summary: This review provides an in-depth overview of the impact of S-palmitoylation on various cellular processes in macrophages, including protein activity, stability, trafficking, and interactions. It also discusses the therapeutic potential of modulators of S-palmitoylation in immunopathologies.
Article
Biochemistry & Molecular Biology
Jarrett R. Remsberg, Radu M. Suciu, Noemi A. Zambetti, Thomas W. Hanigan, Ari J. Firestone, Anagha Inguva, Amanda Long, Nhi Ngo, Kenneth M. Lum, Cassandra L. Henry, Stewart K. Richardson, Marina Predovic, Ben Huang, Melissa M. Dix, Amy R. Howell, Micah J. Niphakis, Kevin Shannon, Benjamin F. Cravatt
Summary: The covalent inhibitor ABD957 selectively impairs N-Ras depalmitoylation in AML cells, showing potential as a targeted therapy for NRAS-mutant cancers. It acts on dynamically palmitoylated proteins at the plasma membrane, causing partial effects on N-Ras palmitoylation with greater proteome selectivity compared to Palmostatin M. Additionally, ABD957 inhibits N-Ras signaling and AML cell growth, synergizing with MEK inhibition.
NATURE CHEMICAL BIOLOGY
(2021)
Article
Biochemical Research Methods
Sachio Suzuki, Masaru Yoshikawa, Shunsuke Sawada, Neal K. Devaraj, Shinya Tsukiji
Summary: Conjugating small-molecule ligands to synthetic motifs that can localize to specific organelles or membranes is a practical approach to manipulate biological processes. We have developed a synthetic myristoyl-DCys motif that can undergo S-palmitoylation and localize to the Golgi surface. By miniaturizing the myristoyl-DCys motif, we have identified four new derivatives that retain the palmitoylation-dependent Golgi localization property. These miniaturized motifs can be used to generate small-molecule ligand conjugates for protein localization and cell signaling control.
BIOCONJUGATE CHEMISTRY
(2023)
Article
Cell Biology
Mohamed Rasheed Gadalla, Eliot Morrison, Marina Serebryakova, Xueijiao Han, Thorsten Wolff, Christian Freund, Larisa Kordyukova, Michael Veit
Summary: The study revealed that ZDHHC22 is upregulated in virus-infected cells, particularly with avian influenza virus strains. Knocking out ZDHHC22 gene did not reduce acylation of M2 and HA, indicating its potential involvement in virus replication.
CELLULAR MICROBIOLOGY
(2021)
Article
Immunology
Caroline Lanz, Michael Schotsaert, Carsten Magnus, Umut Karakus, Annika Hunziker, Milagros Sempere Borau, Carles Martinez-Romero, Eva E. Spieler, Sira C. Gunther, Eva Moritz, Benjamin G. Hale, Alexandra Trkola, Adolfo Garcia-Sastre, Silke Stertz
Summary: The severity of influenza varies greatly in humans, and the IFITM3 gene is a genetic determinant responsible for these differences. IFITM3 blocks cytosolic entry of influenza A virus by competing with viral hemagglutinin incorporation into virions. This inhibition leads to increased sensitivity of IAV to antibody-mediated neutralization and affects infection outcomes.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Chemistry, Physical
Michal Michalski, Piotr Setny
Summary: Influenza virus enters host cells through membrane fusion, which is facilitated by the viral hemagglutinin protein (HA). Our computational study reveals the important role of the HA C-terminal domain in fusion, shedding light on its structural and functional interdependencies.
JOURNAL OF PHYSICAL CHEMISTRY B
(2023)
Article
Biochemistry & Molecular Biology
Consuelo Coronel Arrechea, Maria Luz Giolito, Iris Alejandra Garcia, Gaston Soria, Javier Valdez Taubas
Summary: Protein palmitoylation, a common post-translational modification, plays important roles in various cancers, neurodegenerative diseases, and infectious diseases. Lack of specific inhibitors has hampered research progress in this field. A yeast-based high-throughput method has been developed to screen for small molecules that inhibit protein palmitoylation effectively.
Article
Biochemistry & Molecular Biology
Emma H. Garst, Hwayoung Lee, Tandrila Das, Shibani Bhattacharya, Avital Percher, Rafal Wiewiora, Isaac P. Witte, Yumeng Li, Tao Peng, Wonpil Im, Howard C. Hang
Summary: Site-specific S-palmitoylation of IFITM3 enhances its antiviral activity by modulating its conformation and interaction with lipid membranes, demonstrating the direct impact of lipidation on the protein's biophysical properties and cellular activity to prevent virus infection.
ACS CHEMICAL BIOLOGY
(2021)
Article
Biophysics
Annett Petrich, Valentin Dunsing, Sara Bobone, Salvatore Chiantia
Summary: The study found that M2 recruits M1 to the plasma membrane through a strong interaction between the two proteins, while there is only a weak interaction between M1 and HA, which occurs only when M1 is already bound to the plasma membrane.
BIOPHYSICAL JOURNAL
(2021)
Article
Microbiology
Titus Abiola Olukitibi, Zhujun Ao, Hiva Azizi, Mona Mahmoudi, Kevin Coombs, Darwyn Kobasa, Gary Kobinger, Xiaojian Yao
Summary: This study reveals the efficacy of a novel influenza vaccine candidate based on Ebola glycoprotein dendritic cell-targeting domain. The vaccine candidate efficiently targets immune cells and induces high titers of antibodies, providing protection against different influenza strains.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Xu Zhang, Tim Abel, Shuo Su, Andreas Herrmann, Kai Ludwig, Michael Veit
Summary: The assembly and budding of influenza C virus is mediated by three membrane proteins. The hexagonal arrangement of the HEF protein is crucial for virus budding, and its interaction with CM1 stabilizes the clusters. CM2 and CM1 also play important roles in this process.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Virology
David Francis Burke
Summary: The genetic basis of antigenic drift of human A/H3N2 influenza virus is crucial to understanding the constraints of influenza evolution and determinants of vaccine escape. Amino acid changes at only seven positions near the receptor binding site of the surface hemagglutinin protein have been shown to be responsible for the major antigenic changes for over forty years. Experimental structures of HA are now available for the majority of the observed antigenic clusters of A/H3N2, providing a structural basis for the antigenic changes seen in human influenza viruses.
Article
Chemistry, Multidisciplinary
Elizabeth R. Webster, Katherine N. Liu, Robert J. Rawle, Steven G. Boxer
Summary: This study investigates the impact of receptor length and rigidity on the mechanism of influenza virus entry. The results suggest that shorter and more flexible receptors increase the binding rate of the virus, while longer and more rigid receptors decrease the efficiency of lipid and content mixing.
Article
Biochemistry & Molecular Biology
Xu Zhang, Tim Abel, Shuo Su, Andreas Herrmann, Kai Ludwig, Michael Veit
Summary: The assembly and budding of influenza C virus is mediated by three membrane proteins. The hexagonal arrangement of the HEF protein is crucial for virus budding, and its interaction with CM1 stabilizes the clusters. CM2 and CM1 also play important roles in this process.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Virology
Ningning Wang, Xiaofeng Zhai, Xiaoling Li, Yu Wang, Wan-Ting He, Zhiwen Jiang, Michael Veit, Shuo Su
Summary: The lack of monitoring and vaccines has led to widespread infections of alphaviruses. Getah virus (GETV), a mosquito-borne alphavirus, poses a risk to animals and potentially humans. The identification of residue 253 in the E2 glycoprotein as crucial for viral infection and pathogenesis highlights the importance of understanding the genetic determinants of GETV virulence. The discovery of heparan sulfate (HS) as an attachment factor for GETV, along with the potential for targeted therapies based on residue 253, reveals new insights into the pathogenic mechanisms and treatment options for GETV.
JOURNAL OF VIROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Irina Panina, Nikolay Krylov, Mohamed Rasheed Gadalla, Elena Aliper, Larisa Kordyukova, Michael Veit, Anton Chugunov, Roman Efremov
Summary: Lipid modification of viral proteins plays a crucial role in virus pathogenesis. The study focuses on human DHHC20 enzyme involved in S-protein acylation of SARS-CoV-2. Molecular dynamics simulations reveal that C16 is the preferred acyl chain length for autoacylation by hDHHC20, although the V185G mutant shows preference for C18. Unusual hydrophilic ridge and responsive hydrophilic patch in hDHHC20 and S-protein TM-domain trimer respectively are also found. Mutations in critical residues of the spike protein result in decreased S-acylation. The findings may contribute to the development of inhibitors targeting hDHHC20 for interfering with replication of coronaviruses and other enveloped viruses.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Ekaterina Ilgova, Simon Galkin, Maria Khrenova, Marina Serebryakova, Marina Gottikh, Andrey Anisenko
Summary: This study identified key residues I72, S73, and I76 of Ku70 protein as essential for integrase binding using a peptide fishing assay and site-directed mutagenesis. Molecular dynamics studies revealed a possible mechanism for the interaction between integrase and Ku70. Compounds that inhibit the formation of the integrase complex with Ku70 were identified and confirmed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Virology
Anna Karolina Matczuk, Minze Zhang, Michael Veit, Maciej Ugorski
Summary: Equine arteritis virus (EAV) is a significant pathogen of horses, with its glycoproteins GP2, GP3, and GP4 forming a heterotrimer complex responsible for cellular tropism, making it a potential subunit vaccine candidate for horses.
Review
Cell Biology
Jin Tian, Jiumeng Sun, Dongyan Li, Ningning Wang, Lifang Wang, Chang Zhang, Xiaorong Meng, Xiang Ji, Marc A. Suchard, Xu Zhang, Alexander Lai, Shuo Su, Michael Veit
Summary: This article mainly introduces the taxonomy, geographic distribution, and unique traits of bats as virus reservoirs, as well as the origin, intermediate hosts, and interspecies transmission mechanisms of Middle East respiratory syndrome coronavirus, severe acute respiratory syndrome coronavirus, SARS-CoV-2, and other viruses associated with bats. The molecular interactions between viral surface proteins and host cell receptors are also studied, comparing these interactions in humans, intermediate hosts, and bats.
Article
Biochemistry & Molecular Biology
Michael Veit, Mohamed Rasheed Gadalla, Minze Zhang
Summary: This study used the artificial intelligence-based system alphafold2 to predict the structure of Gp5/M in porcine reproductive and respiratory syndrome virus. The predicted structure revealed a dimeric core and an open cavity beneath the membrane, and showed similarities to the M and Orf3a proteins of coronaviruses. The study also discussed the role of Gp5/M in virus replication and the mechanisms of antibody-dependent virus neutralization.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Irina S. Panina, Nikolay A. Krylov, Anton O. Chugunov, Roman G. Efremov, Larisa V. Kordyukova
Summary: S-acylation is an important post-translational modification that links long chain fatty acids to cysteines. This process is catalyzed by a family of 23 membrane DHHC-acyltransferases in human cells. In this study, the researchers used molecular dynamics simulations to investigate the structure of membrane-bound hDHHC20 before acylation by different chain length acyl-CoA substrates. The results showed that regardless of the chain length, the terminal methyl group of the substrate always reaches the ceiling of the enzyme's cavity. Only C16 showed optimal reactivity for autoacylation. These findings provide insights into the specific recognition of acyl-CoA substrates by DHHC-acyltransferases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Letter
Infectious Diseases
Jiumeng Sun, Ningning Wang, Zhiwen Jiang, Dongyan Li, Jin Zhao, Xinxin Li, Lang Gong, Chang Zhang, Haijian He, Shuo Su, Guihong Zhang, Michael Veit
JOURNAL OF INFECTION
(2023)
Article
Virology
Jin Zhao, Simon Dellicour, Ziqing Yan, Michael Veit, Mandev S. Gill, Wan-Ting He, Xiaofeng Zhai, Xiang Ji, Marc A. Suchard, Philippe Lemey, Shuo Su
Summary: By conducting metagenomic next-generation sequencing, we identified Getah virus as the pathogen responsible for a reemerging swine disease in China. This virus is capable of replicating in various cell lines, including human cells, and demonstrates high pathogenicity in a mouse model. Our study also revealed the impact of environmental factors on the genetic diversity and dispersal of the virus.
JOURNAL OF VIROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Victor Vitoldovich Poboinev, Vladislav Victorovich Khrustalev, Anastasia Aleksandrovna Akunevich, Nikolai Vladimirovich Shalygo, Aleksander Nikolaevich Stojarov, Tatyana Aleksandrovna Khrustaleva, Larisa Valentinovna Kordyukova
Summary: Researchers have studied the cytoplasmic domain of the influenza virus hemagglutinin (HA) and found that its beta structure is determined by its amino acid sequence rather than aggregation. They have also identified tripeptides that can block the interaction between HA CT and M1 protein.
Article
Virology
Larisa V. Kordyukova, Andrey V. Moiseenko, Marina V. Serebryakova, Marina A. Shuklina, Maria V. Sergeeva, Dmitry A. Lioznov, Andrei V. Shanko
Summary: In this study, different methods for inactivating the SARS-CoV-2 virus were compared, and it was found that beta-propiolactone, formaldehyde, and UV radiation can successfully inactivate the virus. The study also found that the beta-propiolactone-inactivated samples had a higher abundance of needle-like proteins on the viral surface. Mass spectrometry analysis detected the structural proteins of SARS-CoV-2. The results showed that the formaldehyde and UV-inactivated samples had the highest immunoreactivity against convalescent sera, while the beta-propiolactone and UV-inactivated samples showed stronger immunoreactivity against sera from people vaccinated with Sputnik V.
Article
Virology
Xiaorong Meng, Michael Veit
Summary: This study found that the palmitoylation of HA of influenza B virus occurs in the ER, whereas acylation of HA of influenza A virus occurs in the Golgi. The ER-localized DHHCs 1, 2, 4, and 6 are responsible for acylation of HA of influenza B virus, which is different from the enzymes identified for acylation of HA of influenza A virus. The transmembrane region may be critical for the acylation of HA of influenza A and B viruses by different DHHCs.
JOURNAL OF VIROLOGY
(2023)
Article
Virology
Wan-Ting He, Dongyan Li, Guy Baele, Jin Zhao, Zhiwen Jiang, Xiang Ji, Michael Veit, Marc A. Suchard, Edward C. Holmes, Philippe Lemey, Maciej F. Boni, Shuo Su
Summary: Through retrospective epidemiological study, new lineages of porcine hemagglutinating encephalomyelitis virus (PHEV) complex coronaviruses (CoVs) were discovered in swine populations in China. These novel lineages cause respiratory symptoms without neurological symptoms typically associated with classical PHEV infection. The novel lineages have been circulating in at least eight provinces in southeastern China.