Version 1
: Received: 21 February 2018 / Approved: 21 February 2018 / Online: 21 February 2018 (16:57:27 CET)
How to cite:
Ul-Haq, Z.; Ali, N.; Al-Agamy, M.H.; Barakat, A. Structural and Functional Characterization of RNA-binding Site of Rev and Rev-Response-Element RNA Complex via All Atom Molecular Dynamics Simulations. Preprints2018, 2018020138. https://doi.org/10.20944/preprints201802.0138.v1
Ul-Haq, Z.; Ali, N.; Al-Agamy, M.H.; Barakat, A. Structural and Functional Characterization of RNA-binding Site of Rev and Rev-Response-Element RNA Complex via All Atom Molecular Dynamics Simulations. Preprints 2018, 2018020138. https://doi.org/10.20944/preprints201802.0138.v1
Ul-Haq, Z.; Ali, N.; Al-Agamy, M.H.; Barakat, A. Structural and Functional Characterization of RNA-binding Site of Rev and Rev-Response-Element RNA Complex via All Atom Molecular Dynamics Simulations. Preprints2018, 2018020138. https://doi.org/10.20944/preprints201802.0138.v1
APA Style
Ul-Haq, Z., Ali, N., Al-Agamy, M.H., & Barakat, A. (2018). Structural and Functional Characterization of RNA-binding Site of Rev and Rev-Response-Element RNA Complex via All Atom Molecular Dynamics Simulations. Preprints. https://doi.org/10.20944/preprints201802.0138.v1
Chicago/Turabian Style
Ul-Haq, Z., Mohamed H. Al-Agamy and Assem Barakat. 2018 "Structural and Functional Characterization of RNA-binding Site of Rev and Rev-Response-Element RNA Complex via All Atom Molecular Dynamics Simulations" Preprints. https://doi.org/10.20944/preprints201802.0138.v1
Abstract
Nuclear export of viral mRNAs, is an essential step in the HIV replication cycle. This role is played by a small regulatory protein of HIV-1 called Rev.The N-terminal region of Rev contains an arginine-rich sequence. The arginine-rich motif (ARM) is located between amino acids 38-50 and forms an alpha-helical secondary structure. Expression of the structural proteins of human immunodeficiency virus type 1 requires the direct interaction of multiple copies of the viral Rev protein with its highly structured RNA target sequence, the Rev Response element (RRE). The major viral proteins are not produced if this transport of RNA is stopped. Therefore, knowledge of Rev structure is essential for understanding of its cooperative binding to the RRE, for understanding the mechanism of HIV infection and for the development of antiviral drugs that interfere with Rev’s essential functions and for acknowledgment of good candidate drugs for treatment of AIDS. To understand how REV interact with RRE element of HIV-RNA and its formation of oligomeric complex it is better to characterize the domain wise structure of REV with regard in function of each domain. Due to lack of structural data on Rev no single compound is reported as inhibitor of REV expect antiviral drugs. Identification of a high-affinity RNA-binding site for the human immunodeficiency virus type 1 Rev Protein is much more important. The ARM is a highly specific sequence which allows for the multimerization of Rev and also binding of REV with RNA. Here we are first time exploring the structural characteristics of REV protein both in free form and in complex with RNA at domain function level especially explore the role of ARM motif in REV HIV-1 protein as RNA binding sites by molecular dynamics (MD) simulation and homology modeling studies. Results indicate that the arginine-rich motif (ARM) is crucial in stability of this complex. The residues ARG38, 39, 41, 43, 44, 48, 50, and ASN40 are most interacting with nucleobases of RRE in Crystal structure of Rev and Rev-response-element RNA complex. Our study plays a major role in elaboration of binding of RNA with REV and pave the way for further investigation for therapeutically agent for HIV.
Copyright:
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