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Molecular coevolution of nuclear and nucleolar localization signals inside basic domain of HIV-1 Tat
- Source :
- J Virol, Journal of Virology, Journal of Virology, American Society for Microbiology, 2021, ⟨10.1128/jvi.01505-21⟩
- Publication Year :
- 2021
- Publisher :
- HAL CCSD, 2021.
-
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, reduces protein size, influencing the origin and evolution of NLSs and NoLSs in viruses. IMPORTANCE Here, we investigated the molecular mechanism of nuclear localization signal (NLS) and nucleolar localization signal (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 function of 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.
- Subjects :
- Signal peptide
Gene Expression Regulation, Viral
Models, Molecular
Nucleolus
[SDV]Life Sciences [q-bio]
Immunology
Nuclear Localization Signals
HIV Infections
Biology
Microbiology
Evolution, Molecular
Transactivation
03 medical and health sciences
Structure-Activity Relationship
Viral Proteins
Transcription (biology)
Virology
Consensus Sequence
medicine
NLS
Protein Interaction Domains and Motifs
Amino Acid Sequence
Peptide sequence
030304 developmental biology
chemistry.chemical_classification
Cell Nucleus
0303 health sciences
Binding Sites
030302 biochemistry & molecular biology
Amino acid
Cell biology
Virus-Cell Interactions
Cell nucleus
Protein Transport
medicine.anatomical_structure
chemistry
Insect Science
Viral evolution
Host-Pathogen Interactions
HIV-1
tat Gene Products, Human Immunodeficiency Virus
Function (biology)
Nuclear localization sequence
Cell Nucleolus
Protein Binding
Subjects
Details
- Language :
- English
- ISSN :
- 0022538X and 10985514
- Database :
- OpenAIRE
- Journal :
- J Virol, Journal of Virology, Journal of Virology, American Society for Microbiology, 2021, ⟨10.1128/jvi.01505-21⟩
- Accession number :
- edsair.doi.dedup.....3c215b021275400d1bc78aa41ece081b