Structural modeling of protein ensembles between E3 RING ligases and SARS-CoV-2: The role of zinc binding domains |
| |
Affiliation: | 1. Institute of Chemical Biology, National Hellenic Research Foundation, 11635 Athens, Greece;2. Department of Chemistry, University of Patras, Patras 26504, Greece;3. Council for Nutritional and Environmental Medicine (CONEM), Mo i Rana, Norway;4. Department of Chemical, Physical, Mathematical and Natural Sciences, University of Sassari, Italy |
| |
Abstract: | BackgroundThe ubiquitin system is a modification process with many different cellular functions including immune signaling and antiviral functions. E3 ubiquitin ligases are enzymes that recruit an E2 ubiquitin-conjugating enzyme bound to ubiquitin in order to catalyze the transfer of ubiquitin from the E2 to a protein substrate. The RING E3s, the most abundant type of ubiquitin ligases, are characterized by a zinc (II)-binding domain called RING (Really Interesting New Gene). Viral replication requires modifying and hijacking key cellular pathways within host cells such as cellular ubiquitination. There are well-established examples where a viral proteins bind to RING E3s, redirecting them to degrade otherwise long-lived host proteins or inhibiting E3’s ubiquitination activity. Recently, three binary interactions between SARS-CoV-2 proteins and innate human immune signaling Ε3 RING ligases: NSP15-RNF41, ORF3a-TRIM59 and NSP9-MIB1 have been experimentally established.MethodsIn this work, we have investigated the mode of the previous experimentally supported NSP15-RNF41, ORF3a,-TRIM59 and NSP9-MIB1 binary interactions by in silico methodologies intending to provide structural insights of E3-virus interplay that can help identify potential inhibitors that could block SARS-CoV-2 infection of immune cells.ConclusionIn silico methodologies have shown that the above human E3 ligases interact with viral partners through their Zn(II) binding domains. This RING mediated formation of stable SARS-CoV-2-E3 complexes indicates a critical structural role of RING domains in immune system disruption by SARS-CoV-2-infection.Data AvailabilityThe data used to support the findings of this research are included within the article and are labeled with references. |
| |
Keywords: | E3 RING ligases SARS-CoV-2 Zinc binding RING domains Haddock |
本文献已被 ScienceDirect 等数据库收录! |
|