Skip to Main content Skip to Navigation
Journal articles

Molecular coevolution of nuclear and nucleolar localization signals inside basic domain of HIV-1 Tat

Abstract : During evolution, viruses had to adapt to an increasingly complex environment of eukaryotic cells. Viral proteins that need to enter the cell nucleus or associate with nucleoli possess nuclear localization signals (NLSs) and nucleolar localization signals (NoLSs) for nuclear and nucleolar accumulation, respectively. As viral proteins are relatively small, acquisition of novel sequences seems to be a more complicated task for viruses than for eukaryotes. Here, we carried out a comprehensive analysis of the basic domain (BD) of HIV-1 Tat to show how viral proteins might evolve with NLSs and NoLSs without an increase in protein size. The HIV-1 Tat BD is involved in several functions, the most important being the transactivation of viral transcription. The BD also functions as an NLS, although it is substantially longer than a typical NLS. It seems that different regions in the BD could function as NLSs due to its enrichment with positively charged amino acids. Additionally, the high positive net charge inevitably causes the BD to function as an NoLS through a charge-specific mechanism. The integration of NLSs and NoLSs into functional domains enriched with positively charged amino acids might be a mechanism that allows the condensation of different functional sequences in small protein regions and, as a result, to reduce protein size, influencing the origin and evolution of NLSs and NoLSs in viruses. IMPORTANCE Here, we investigated the molecular mechanism of NLS and NoLS integration into the basic domain of HIV-1 Tat ( 49 RKKRRQRRR 57 ), and found that these two supplementary functions (i.e., function of NLS and NoLS) are embedded in the basic domain amino acid sequence. The integration of NLSs and NoLSs into functional domains of viral proteins enriched with positively charged amino acids is a mechanism that allows the concentration of different functions within small protein regions. Integration of NLS and NoLS into functional protein domains might have influenced the viral evolution, as this could prevent an increase in the protein size.
Document type :
Journal articles
Complete list of metadata

https://hal.archives-ouvertes.fr/hal-03376023
Contributor : Yegor Vassetzky Connect in order to contact the contributor
Submitted on : Saturday, October 16, 2021 - 1:46:40 PM
Last modification on : Thursday, October 21, 2021 - 5:15:21 AM

File

2021 Kurnaeva JV.pdf
Files produced by the author(s)

Identifiers

Citation

Margarita Kurnaeva, Arthur Zalevsky, Eugene Arifulin, Olga Lisitsyna, Anna Tvorogova, et al.. Molecular coevolution of nuclear and nucleolar localization signals inside basic domain of HIV-1 Tat. Journal of Virology, American Society for Microbiology, 2021, ⟨10.1128/jvi.01505-21⟩. ⟨hal-03376023⟩

Share

Metrics

Record views

15

Files downloads

10