Selected article for: "acid binding and llps liquid liquid phase separation"
Author: Caruso, Icaro Putinhon; dos Santos Almeida, Vitor; Juliani do Amaral, Mariana; de Andrade, Guilherme Caldas; de Araújo, Gabriela Rocha; de Araújo, Talita Stelling; de Azevedo, Jéssica Moreira; Barbosa, Glauce Moreno; Bartkevihi, Leonardo; Bezerra, Peter Reis; dos Santos Cabral, Katia Maria; Lourenço, Isabella Otênio; Malizia-Motta, Clara L. F.; de Luna Marques, Aline; Mebus-Antunes, Nathane Cunha; Neves-Martins, Thais Cristtina; de Sá, Jéssica Maróstica; Sanches, Karoline; Santana-Silva, Marcos Caique; Vasconcelos, Ariana Azevedo; da Silva Almeida, Marcius; de Amorim, Gisele Cardoso; Anobom, Cristiane Dinis; Da Poian, Andrea T.; Gomes-Neto, Francisco; Pinheiro, Anderson S.; Almeida, Fabio C. L.
Title: Structure insights, thermodynamic profiles, dsDNA melting activity, and liquid-liquid phase separation of the SARS-CoV-2 nucleocapsid N-terminal domain binding to DNA
  • Cord-id: eu7cggrz
  • Document date: 2021_7_22
    • ID: eu7cggrz
    Snippet: The SARS-CoV-2 nucleocapsid protein (N) is a multifunctional promiscuous nucleic acid-binding protein, which plays a major role in nucleocapsid assembly and discontinuous RNA transcription, facilitating the template switch of transcriptional regulatory sequences (TRS). Here, we dissect the structural features of the N protein N-terminal domain (N-NTD), either with or without the SR-rich motif (SR), upon binding to single and double-stranded TRS DNA, as well as their activities for dsTRS melting
    Document: The SARS-CoV-2 nucleocapsid protein (N) is a multifunctional promiscuous nucleic acid-binding protein, which plays a major role in nucleocapsid assembly and discontinuous RNA transcription, facilitating the template switch of transcriptional regulatory sequences (TRS). Here, we dissect the structural features of the N protein N-terminal domain (N-NTD), either with or without the SR-rich motif (SR), upon binding to single and double-stranded TRS DNA, as well as their activities for dsTRS melting and TRS-induced liquid-liquid phase separation (LLPS). Our study gives insights on specificity for N-NTD/N-NTD-SR interaction with TRS, including an unfavorable energetic contribution to binding along with hydrogen bonds between the triple-thymidine (TTT) motif in the dsTRS and β-sheet II due to the defined position and orientation of the DNA duplex, a well-defined pattern (ΔH > 0 and ΔS > 0 for ssTRS, and ΔH < 0 and ΔS < 0 for dsTRS) for the thermodynamic profile of binding, and a preference for TRS in the formation of liquid condensates when compared to a non-specific sequence. Moreover, our results on DNA binding may serve as a starting point for the design of inhibitors, including aptamers, against N, a possible therapeutic target essential for the virus infectivity.

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