Highly ordered clustering of TNFα and BAFF ligand-receptor-adaptor complexes bound to lipid membranes DOI Creative Commons

Chan Seok Lim,

Jisun Lee, Ji Won Kim

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июль 23, 2024

SUMMARY We report the cryo-EM structures of clusters TNF receptor family proteins, TNFR1 and BAFFR. The receptor-ligand complexes were anchored to a flat lipid layer mimic membrane-bound state. observed that TNFα-TNFR1 complex forms highly ordered binary, bent, trigonal, linear quadruple trimers on membrane. A non-competitive antagonist disrupted these without interfering with ligand binding. Moreover, we found BAFF-BAFFR pentagonal, double-pentagonal, or half-spherical trimers. Mutations in BAFF inhibit BAFFR activation prevented clustering disrupting TRAF3 induced structural shift cluster, resulting hexagonal cluster. Our data demonstrated precisely structured is essential for receptors. monolayer method will aid studying other transmembrane proteins facilitate discovery therapeutic agents regulate their clustering.

Язык: Английский

SARS-CoV-2 ORF3a Protein as a Therapeutic Target against COVID-19 and Long-Term Post-Infection Effects DOI Creative Commons
Jiantao Zhang,

Kellie Hom,

Chen‐Yu Zhang

и другие.

Pathogens, Год журнала: 2024, Номер 13(1), С. 75 - 75

Опубликована: Янв. 14, 2024

The COVID-19 pandemic caused by SARS-CoV-2 has posed unparalleled challenges due to its rapid transmission, ability mutate, high mortality and morbidity, enduring health complications. Vaccines have exhibited effectiveness, but their efficacy diminishes over time while new variants continue emerge. Antiviral medications offer a viable alternative, success been inconsistent. Therefore, there remains an ongoing need identify innovative antiviral drugs for treating post-infection ORF3a (open reading frame 3a) protein found in SARS-CoV-2, represents promising target treatment multifaceted role viral pathogenesis, cytokine storms, disease severity, mortality. contributes significantly pathogenesis facilitating assembly release, essential processes the life cycle, also suppressing body’s responses, thus aiding replication. implicated triggering excessive inflammation, characterized NF-κB-mediated production, ultimately leading apoptotic cell death tissue damage lungs, kidneys, central nervous system. Additionally, triggers activation of NLRP3 inflammasome, inciting storm, which is major contributor severity subsequent As with spike protein, undergoes mutations, certain mutant correlate heightened COVID-19. These mutations may influence replication host cellular inflammatory responses. While establishing direct link between difficult, involvement promoting inflammation exacerbating likely higher rates severe cases. This review offers comprehensive detailed exploration ORF3a’s potential as drug target. we outline strategies discovering developing inhibitor counteract harmful effects, alleviate damage, reduce lingering

Язык: Английский

Процитировано

7
A live attenuated SARS-CoV-2 vaccine constructed by dual inactivation of NSP16 and ORF3a DOI
Zi‐Wei Ye, Chon Phin Ong,

Hehe Cao

и другие.

EBioMedicine, Год журнала: 2025, Номер 114, С. 105662 - 105662

Опубликована: Март 25, 2025

Язык: Английский

Процитировано

0
Highly ordered clustering of TNFα and BAFF ligand-receptor-adaptor complexes bound to lipid membranes DOI Creative Commons

Chan Seok Lim,

Jisun Lee, Ji Won Kim

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июль 23, 2024

SUMMARY We report the cryo-EM structures of clusters TNF receptor family proteins, TNFR1 and BAFFR. The receptor-ligand complexes were anchored to a flat lipid layer mimic membrane-bound state. observed that TNFα-TNFR1 complex forms highly ordered binary, bent, trigonal, linear quadruple trimers on membrane. A non-competitive antagonist disrupted these without interfering with ligand binding. Moreover, we found BAFF-BAFFR pentagonal, double-pentagonal, or half-spherical trimers. Mutations in BAFF inhibit BAFFR activation prevented clustering disrupting TRAF3 induced structural shift cluster, resulting hexagonal cluster. Our data demonstrated precisely structured is essential for receptors. monolayer method will aid studying other transmembrane proteins facilitate discovery therapeutic agents regulate their clustering.

Язык: Английский

Процитировано

1