Abstract
BackgroundRev-like proteins are post-transcriptional regulatory proteins found in several retrovirus genera, including lentiviruses, betaretroviruses, and deltaretroviruses. These essential proteins mediate the nuclear export of incompletely spliced viral RNA, and act by tethering viral pre-mRNA to the host CRM1 nuclear export machinery. Although all Rev-like proteins are functionally homologous, they share less than 30% sequence identity. In the present study, we computationally assessed the extent of structural homology among retroviral Rev-like proteins within a phylogenetic framework.ResultsWe undertook a comprehensive analysis of overall protein domain architecture and predicted secondary structural features for representative members of the Rev-like family of proteins. Similar patterns of α-helical domains were identified for Rev-like proteins within each genus, with the exception of deltaretroviruses, which were devoid of α-helices. Coiled-coil oligomerization motifs were also identified for most Rev-like proteins, with the notable exceptions of HIV-1, the deltaretroviruses, and some small ruminant lentiviruses. In Rev proteins of primate lentiviruses, the presence of predicted coiled-coil motifs segregated within specific primate lineages: HIV-1 descended from SIVs that lacked predicted coiled-coils in Rev whereas HIV-2 descended from SIVs that contained predicted coiled-coils in Rev. Phylogenetic ancestral reconstruction of coiled-coils for all Rev-like proteins predicted a single origin for the coiled-coil motif, followed by three losses of the predicted signal. The absence of a coiled-coil signal in HIV-1 was associated with replacement of canonical polar residues with non-canonical hydrophobic residues. However, hydrophobic residues were retained in the key ‘a’ and ‘d’ positions, and the α-helical region of HIV-1 Rev oligomerization domain could be modeled as a helical wheel with two predicted interaction interfaces. Moreover, the predicted interfaces mapped to the dimerization and oligomerization interfaces in HIV-1 Rev crystal structures. Helical wheel projections of other retroviral Rev-like proteins, including endogenous sequences, revealed similar interaction interfaces that could mediate oligomerization.ConclusionsSequence-based computational analyses of Rev-like proteins, together with helical wheel projections of oligomerization domains, reveal a conserved homogeneous structural basis for oligomerization by retroviral Rev-like proteins.
Highlights
Rev-like proteins are post-transcriptional regulatory proteins found in several retrovirus genera, including lentiviruses, betaretroviruses, and deltaretroviruses
Rev‐like proteins share a similar functional organization To determine whether the overall architecture of Revlike proteins follows a conserved structural pattern, we compared the organization of protein domains of representative Rev-like members of lentiviruses, deltaretroviruses and betaretroviruses
Rev-like proteins vary in length, a similar organization of protein domains in which the Nuclear Export Signal (NES) is located C-terminal to the arginine-rich motif (ARM) was observed in all members except Equine infectious anemia virus (EIAV) Rev (Fig. 1, left)
Summary
Rev-like proteins are post-transcriptional regulatory proteins found in several retrovirus genera, including lentiviruses, betaretroviruses, and deltaretroviruses. Lentiviruses encode the regulatory protein Rev [1,2,3,4,5,6,7,8,9]; deltaretroviruses encode a Rev analog, Rex [10, 11]; and three betaretroviruses, mouse mammary tumor virus (MMTV), Jaagsitke sheep retrovirus (JSRV), and the human endogenous retrovirus type K (HERV-K HML2), encode the regulatory proteins Rem [12, 13], Rej [14], and Rec, respectively [15] This family of proteins, collectively termed Rev-like proteins, is believed to share a similar mechanism of function despite being highly divergent at the sequence level. Specific motifs or domains in HIV-1 Rev and other Rev-like proteins mediate distinct steps of the Rev pathway, including nuclear import, RNA binding, oligomerization and nuclear export [18,19,20,21]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
