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Zn-Induced Interactions Between SARS-CoV-2 orf7a and BST2/Tetherin
Maria Petrosino1, Francesco Stellato2,3, Roberta Chiaraluce1
1Dipartimento di Scienze Biochimiche "A. Rossi Fanelli", Sapienza Università di Roma, Piazzale Aldo Moro 5, 00185, Roma, Italy.
Zinc binds to BST2 and SARS-CoV-2 orf7a proteins, forming complexes that impair BST2
Area of Science:
- Structural biology
- Virology
- Biochemistry
Background:
- BST2/tetherin is an antiviral protein crucial for innate immunity.
- SARS-CoV-2 orf7a is a viral accessory protein implicated in immune evasion.
- The interaction between BST2 and SARS-CoV-2 proteins is not fully understood.
Purpose of the Study:
- To investigate the interaction between zinc, BST2, and SARS-CoV-2 orf7a.
- To elucidate the structural mechanisms underlying the interference of orf7a with BST2 antiviral activity.
Main Methods:
- X-ray Absorption Spectroscopy (XAS) was employed to study zinc binding.
- Analysis focused on the XANES region of the XAS spectra.
- Complex formation between BST2 and orf7a was investigated.
Main Results:
- XAS data confirmed zinc binding to both BST2 and orf7a.
- The formation of BST2-orf7a complexes was observed.
- A mechanism involving zinc displacement and disulfide bridge formation was proposed.
Conclusions:
- Zinc binding facilitates the interaction between BST2 and orf7a.
- The BST2-orf7a complex formation destabilizes BST2, impairing its antiviral function.
- This study provides structural insights into SARS-CoV-2's interference with BST2.
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