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Probing the influence of hypermodified residues within the tRNA3Lys anticodon stem loop interacting with the A-loop primer sequence from HIV-1
- Source :
- Biochimica et Biophysica Acta (BBA) - General Subjects. 1860:607-617
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
Abstract
- Replication of the HIV-1 virus requires reverse transcription of the viral RNA genome, a process that is specifically initiated by human tRNA3(Lys) packaged within the infectious virion. The primary binding site for the tRNA involves the 3' 18 nucleotides with an additional interaction between an adenine rich loop (A-loop) in the template and the anticodon stem-loop region of the tRNA3(Lys). The loop of the tRNA primer contains two hypermodified base residues and a pseudouridine that are required for a proper binding and activity. Here, we investigate the influence on the structure, dynamics and binding stability of the three modified residues (mnm(5)s(2)U34, t(6)A37 and Ψ39) using extensive molecular dynamics and Quantum Theory of Atoms in Molecules (QTAIM) analysis. Consistent with experiment, the results suggest that the three modified residues are required for faithful binding. Residues mnm(5)s(2)U34 and Ψ39 have a major influence in stabilizing the anticodon loop whereas mnm(5)s(2)U34 and t(6)A37 appear to stabilize the formation of the complex of tRNA3(Lys) with the HIV-1 A-loop.
- Subjects :
- 0301 basic medicine
Stereochemistry
Biophysics
Electrons
Sequence (biology)
Molecular dynamics
Biology
Quantum mechanics
01 natural sciences
Biochemistry
Pseudouridine
03 medical and health sciences
chemistry.chemical_compound
HIV genome
0103 physical sciences
Anticodon
Nucleotide
Binding site
tRNA
Molecular Biology
DNA Primers
chemistry.chemical_classification
010304 chemical physics
Anti-codon loop
Stem-loop
HIV transcription
Reverse transcriptase
3. Good health
030104 developmental biology
QTAIM
chemistry
Transfer RNA
HIV-1
RNA, Transfer, Lys
RNA dynamics
Primer (molecular biology)
Subjects
Details
- ISSN :
- 03044165
- Volume :
- 1860
- Database :
- OpenAIRE
- Journal :
- Biochimica et Biophysica Acta (BBA) - General Subjects
- Accession number :
- edsair.doi.dedup.....d5f6b0be08fb88cb89ab43ef8f37f727