Moderate Binding between Two SARS-CoV-2 Protein Segments and α-Synuclein Alters Its Toxic Oligomerization Propensity Differently

• DOI: 10.1021/acs.jpclett.2c02278
• Publication Date: 2022-11-10T12:17:27Z
• Authors: Vince St. Dollent...; Hongni Zhu; Xiao Tang; Xin Dai; Wei Liu; Yusong Guo; Jinqing Huang
• Keywords: Antiparallel (mathematics); spike protein

The neurological symptoms of long COVID and viral neuroinvasion have raised concerns about the potential interactions between SARS-CoV-2 protein segments neuronal proteins, which might confer a risk post-infection neurodegeneration, but underlying mechanisms remain unclear. Here, we reported that receptor-binding domain (RBD) spike nine-residue segment (SK9) envelope could bind to α-synuclein (αSyn) with Kd values 503 ± 24 nM 12.7 1.6 μM, respectively. RBD inhibit αSyn fibrillization by blocking non-amyloid-β component region mediating its antiparallel β-sheet structural conversions. Omicron-RBD (BA.5) was shown slightly stronger affinity for (Kd = 235 10 nM), implies similar effects, whereas SK9 may C-terminus accelerates formation parallel β-sheet-containing oligomers abruptly increases rate membrane disruption 213%. Our results provide plausible molecular insights into impact oligomerization propensity is associated Parkinson's disease.