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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Biophysical and Dynamic Characterization of Fine-Tuned Binding of the Human Respiratory Syncytial Virus M2-1 Core Domain to Long RNAs

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Caruso, Icaro P. [1, 2, 3, 4] ; Guimaraes, Giovana C. [3] ; Machado, Vitor B. [3] ; Fossey, Marcelo A. [1, 3] ; Willbold, Dieter [5, 6] ; Almeida, Fabio C. L. [2, 4] ; Souza, Fatima P. [1, 3]
Total Authors: 7
[1] IBILCE UNESP, Dept Phys, Sao Jose Do Rio Preto, SP - Brazil
[2] Univ Fed Rio de Janeiro, Natl Ctr Struct Biol & Bioimaging CENABIO, Rio De Janeiro, RJ - Brazil
[3] IBILCE UNESP, Multiuser Ctr Biomol Innovat CMIB, Sao Jose do Rio Preto, SP - Brazil
[4] Univ Fed Rio de Janeiro, Inst Med Biochem Leopoldo Meis IBqM, Natl Ctr Nucl Magnet Resonance Macromol, Rio de Janeiro, RJ - Brazil
[5] Forschungszentrum Julich, Inst Biol Informat Proc Struct Biochem & JuStruct, Julich - Germany
[6] Heinrich Heine Univ Dusseldorf, Inst Phys Biol, Dusseldorf - Germany
Total Affiliations: 6
Document type: Journal article
Source: Journal of Virology; v. 94, n. 23 DEC 2020.
Web of Science Citations: 0

The human respiratory syncytial virus (hRSV) M2-1 protein functions as a processivity and antitermination factor of the viral polymerase complex. Here, the first evidence that the hRSV M2-1 core domain (cdM2-1) alone has an unfolding activity for long RNAs is presented and the biophysical and dynamic characterization of the cdM2-1/RNA complex is provided. The main contact region of cdM2-1 with RNA was the alpha 1-alpha 2-alpha 5-alpha 6 helix bundle, which suffered local conformational changes and promoted the RNA unfolding activity. This activity may be triggered by basepairing recognition. RNA molecules wrap around the whole cdM2-1, protruding their termini over the domain. The alpha 2-alpha 3 and alpha 3-alpha 4 loops of cdM2-1 were marked by an increase in picosecond internal motions upon RNA binding, even though they are not directly involved in the interaction. The results revealed that the cdM2-1/RNA complex originates from a fine-tuned binding, contributing to the unraveling interaction aspects necessary for M2-1 activity. IMPORTANCE The main outcome is the molecular description of the fine-tuned binding of the cdM2-1/RNA complex and the provision of evidence that the domain alone has unfolding activity for long RNAs. This binding mode is essential in the understanding of the function in the full-length protein. Human respiratory syncytial virus (hRSV), an orthopneumovirus, stands out for the unique role of its M2-1 protein as a transcriptional antitermination factor able to increase RNA polymerase processivity. (AU)

FAPESP's process: 10/18169-3 - Investigations of physical chemistry processes related with the binding of environmental relevant heavy metal ions by calix[4]arenes using molecular dynamics simulations
Grantee:Alexandre Suman de Araujo
Support Opportunities: Regular Research Grants
FAPESP's process: 19/08739-1 - Biophysical characterization of the matrix protein from the respiratory syncytial virus
Grantee:Giovana Cavenaghi Guimarães
Support Opportunities: Scholarships in Brazil - Master
FAPESP's process: 18/08900-4 - Study of competitive interaction between steroidal alkaloids and RNA for the transcription anti-termination factor binding site of human respiratory syncytial virus (hRSV)
Grantee:Vitor Brassolatti Machado
Support Opportunities: Scholarships in Brazil - Master
FAPESP's process: 09/53989-4 - Acquisition of a nuclear magnetic resonance spectrometer for studies of biomolecules
Grantee:Raghuvir Krishnaswamy Arni
Support Opportunities: Multi-user Equipment Program