Thermodynamics and solvation dynamics of BIV TAR RNA–Tat peptide interaction

Abstract

The interaction of the trans-activation responsive (TAR) region of bovine immunodeficiency virus (BIV) RNA with the Tat peptide is known to play important role in viral replication. Despite being thoroughly studied through a structural point of view, the nature of binding between BIV TAR RNA and the BIV Tat peptide requires information related to its thermodynamics and the nature of hydration around the TAR-Tat complex. In this context, we carried out the thermodynamic study of binding of the Tat peptide to the BIV TAR RNA hairpin through different calorimetric and spectroscopic measurements. Fluorescence titration of 2-aminopurine tagged BIV TAR RNA with the Tat peptide gives their binding affinity. The isothermal titration calorimetric experiment reveals the enthalpy of binding between BIV TAR RNA and the Tat peptide to be largely exothermic with the value of -11.7 (SEM 0.2) kcal mol(-1). Solvation dynamics measurements of BIV TAR RNA having 2-AP located at the bulge region have been carried out in the absence and presence of the BIV Tat peptide using the time correlated single photon counting technique. The solvent cage around the Tat binding site of RNA appears to be more rigid in the presence of the Tat peptide as compared to the free RNA. The displacement of solvent and ions on RNA due to peptide binding influences the entropic contributions to the total binding energy.

An Evolved RNA Recognition Motif That Suppresses HIV-1 Tat/TAR-Dependent Transcription

“…Both mutations significantly decreased affinity to TBP 6.6 and TBP 6.7, suggesting that the uppermost stem nucleotides directly participates in complex formation. Additionally, we also tested binding to the TAR sequence from the Bovine Immunodeficiency Virus (BIV TAR(53)). This RNA is structurally similar to HIV TAR, but differs in the sequence and size of the loop (4 bases in BIV TAR, versus 6 bases in HIV TAR) and in the nature of the stem-bulge.…”

Estimation of a stronger heparin binding locus in fibronectin domain III14using thermodynamics and molecular dynamics

“…[12][13][14][15][16] Interactions of several peptides such as cell penetrating peptides (CPPs) have also been reported with heparin. [17][18][19][20][21] Since HEP II-heparin interactions can cause or exacerbates pathophysiological conditions, 22 there is a great prospect of developing agents that can block these interactions. However, there are multiple heparin-binding sites spread across HEP II, and in particular III 14 of FN, and therefore identifying the strongest heparin-binding site is critical for therapeutic intervention.…”

Biophysical insight into the heparin‐peptide interaction and its modulation by a small molecule

“…The biophysical parameterization provides one of the best forms of quantification. Over the past years, several efforts have provided the thermodynamic studies on interaction of heparin with various proteins and model peptides, including cell penetrating peptides (CPPs) . Interactions of several peptides such as those composed of polylysines have also been reported with nucleic acids .…”

“…Over the past years, several efforts have provided the thermodynamic studies on interaction of heparin with various proteins and model peptides, including cell penetrating peptides (CPPs) . Interactions of several peptides such as those composed of polylysines have also been reported with nucleic acids . Considering the role of the heparin‐protein interaction in diseases, and possibility of their therapeutic targeting, we need to address fundamental questions such as what is the molecular basis of the heparin‐protein interaction?…”

“…This sequence is found to be conserved in this family of proteins and is known to play an important role in Tat biology. The HIP is also known to bind specifically to several nucleic acids …”