- Ubiquitin and proteasome pathways
- SARS-CoV-2 and COVID-19 Research
- Genetics and Neurodevelopmental Disorders
- Antimicrobial Peptides and Activities
- Immunotherapy and Immune Responses
- Infant Nutrition and Health
- COVID-19 Impact on Reproduction
- Heparin-Induced Thrombocytopenia and Thrombosis
- COVID-19 Clinical Research Studies
- Dermatological and COVID-19 studies
- Glycosylation and Glycoproteins Research
- Animal Virus Infections Studies
- RNA modifications and cancer
- Peptidase Inhibition and Analysis
- Cancer Mechanisms and Therapy
- Cancer Research and Treatments
- Long-Term Effects of COVID-19
Hebrew University of Jerusalem
2020-2024
Abstract Ufmylation is a post-translational modification essential for regulating key cellular processes. A three-enzyme cascade involving E1, E2 and E3 required UFM1 attachment to target proteins. How UBA5 (E1) UFC1 (E2) cooperatively activate transfer still unclear. Here, we present the crystal structure of bound C-terminus UBA5, revealing how interacts with via short linear sequence, not observed in other E1-E2 complexes. We find that has region outside adenylation domain dispensable...
Intramuscularly administered vaccines stimulate robust serum neutralizing antibodies, yet they are often less competent in eliciting sustainable “sterilizing immunity” at the mucosal level. Our study uncovers a strong temporary component of immunity, emanating from intramuscular administration an mRNA vaccine. We show that saliva BNT162b2 vaccinees contains IgA targeting receptor-binding domain (RBD) severe acute respiratory syndrome coronavirus-2 spike protein and demonstrate these IgAs...
The humoral response after the fourth dose of a mRNA vaccine against COVID-19 has not been adequately described in elderly recipients, particularly those exposed previously to SARS-CoV-2. Serum anti-RBD IgG levels (Abbott SARS-CoV-2 II Quant assay) and neutralizing capacities (spike pseudovirus Wuhan Omicron BA.1 variant) were measured third doses among 46 residents (median age 85 years [IQR 81; 89]) an assisted living facility. Among participants never infected by SARS-CoV-2, mean serum RBD...
Class I WW domains are present in many proteins of various functions and mediate protein interactions by binding to short linear PPxY motifs. Tandem often bind peptides with multiple motifs, but the interplay WW–peptide is not always intuitive. The domain–containing oxidoreductase (WWOX) harbors two domains: an unstable WW1 capable stable WW2 that cannot PPxY. domain has been suggested act as a chaperone, underlying mechanism its chaperone activity remains be revealed. Here, we combined NMR,...
Abstract We describe a molecular characterization of the interaction between cancer‐related proteins WWOX and p73. This is mediated by first two WW domains (WW1) PPXY‐motif‐containing region in While phosphorylation Tyr33 association with p73 are known to affect apoptotic activity, quantitative effect on this specific determined here for time. Using ITC fluorescence anisotropy, we measured binding affinity derived peptide, showed that regulated Tyr WW1. Chemical synthesis phosphorylated...
Recent studies on the oral, anaerobic, gram-negative bacterium Fusobacterium nucleatum revealed its presence and involvement in colorectal, esophageal breast cancer. We previously demonstrated that F. binds activates human inhibitory receptors TIGIT CEACAM1 leading to inhibition of T NK cell anti-tumor immunity. was found be bound activated by fusobacterial trimeric autotransporter adhesin CbpF. Here we report generation a recombinant E. coli expressing full-length CbpF efficiently CEACAM1.
Abstract SARS-CoV-2 infection triggers strong antibody response toward Nucleocapsid-Protein (NP), suggesting extracellular presence beyond its intra-virion RNA binding. Interestingly, NP was found to decorate infected and proximal uninfected cell-surfaces. Here, we propose a new mechanism through which on cells contributes COVID-19 pathogenicity. We show that binds cell-surface sulfated linear-glycosaminoglycans by spatial rearrangement of RNA-binding sites facilitated the flexible,...
Abstract Class I WW domains mediate protein interactions by binding short linear PPxY motifs. They occur predominantly as tandem repeats, and their target proteins often contain multiple motifs, but the interplay of WW/peptide is not always intuitive. domain-containing oxidoreductase (WWOX) harbors two domains: unstable WW1 capable binding, well-folded mutated WW2 that cannot bind such considered to act a chaperone, underlying mechanism remains be revealed. Here we combine NMR, ITC...
Background: The efficacy of three doses mRNA vaccine against COVID-19 has been proven, but waning immunity necessitated boosters. antibody response and neutralizing levels reached after the fourth dose have not adequately described for elderly recipients, particularly those exposed to SARS-CoV-2. ability recipients mount a proper immune new variants when repeatedly vaccinated original variant questioned.Methods: This nested case-control study evaluated third among 46 residents (median age 85...
Abstract Fusobacterium nucleatum is an oral pathogen associated with periodontal disease, preterm births and the exacerbation of colorectal, esophageal, pancreatic, breast cancers. F. was previously found to inhibit killing cancer cells by natural killer (NK) tumor infiltrating T inducing NK killing-suppressing receptors TIGIT CEACAM1. In this study, we show that incubation primary human causes cleavage activating CD16, NKp44 NKp46 fusolisin. Fusolisin a fusobacterial outer-membrane,...