9C2H

SARS-CoV-2 Nucleocapsid Dimerization Domain bound to Fab-NP1E9 and Fab-NP3B4

9C2H の概要

• エントリーDOI: 10.2210/pdb9c2h/pdb
• EMDBエントリー: 45157
• 分子名称: Nucleoprotein, Antibody Fab NP3-B4 Heavy Chain (variable region), Antibody Fab NP3-B4 Light Chain (variable region), ... (5 entities in total)
• 機能のキーワード: protein, fab, immunocomplex, viral protein
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2; 詳細
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 157861.78

構造登録者

Landeras-Bueno, S.,Hariharan, C.,Diaz Avalos, R.,Ollmann Saphire, E. (登録日: 2024-05-31, 公開日: 2025-05-14, 最終更新日: 2025-07-30)

主引用文献

Landeras-Bueno, S.,Hariharan, C.,Avalos, R.D.,Norris, A.S.,Snyder, D.T.,Hastie, K.M.,Harkins, S.,Zandonatti, M.,Rajamanickam, R.R.,Olmedillas, E.,Miller, R.,Shresta, S.,Wysocki, V.H.,Saphire, E.O.
Structural stabilization of the intrinsically disordered SARS-CoV-2 N by binding to RNA sequences engineered from the viral genome fragment.
Nat Commun, 16:6521-6521, 2025

PubMed Abstract: The nucleocapsid N is one of four structural proteins of the coronaviruses. Its essential role in genome encapsidation makes it a critical therapeutic target for COVID-19 and related diseases. However, the inherent disorder of full-length N hampers its structural analysis. Here, we describe a stepwise method using viral-derived RNAs to stabilize SARS-CoV-2 N for EM analysis. We identify pieces of RNA from the SARS-CoV-2 genome that promote the formation of structurally homogeneous N dimers, intermediates of assembly, and filamentous capsid-like structures. Building on these results, we engineer a symmetric RNA to stabilize N protein dimers, the building block of high-order assemblies, for EM studies. We combine domain-specific monoclonal antibodies against N with chemical cross-linking mass spectrometry to validate the spatial arrangement of the N domains within the dimer. Additionally, our cryo-EM analysis reveals novel antigenic sites on the N protein. Our findings provide insights into N protein´s architectural and antigenic principles, which can guide design of pan-coronavirus therapeutics.

PubMed: 40664703
DOI: 10.1038/s41467-025-61861-4

実験手法

ELECTRON MICROSCOPY (3.7 Å)