Water, Shape Recognition, Salt Bridges, and Cation–Pi Interactions Differentiate Peptide Recognition of the HIV Rev-Responsive Element

Michael, Lauren A.; Chenault, Jessica A.; Miller, Billy; Knolhoff, Ann M.; Nagan, Maria C.

doi:10.1016/j.jmb.2009.07.047

Cited by 17 publications

(21 citation statements)

References 108 publications

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“…Besides, the low enthalpy change in Rev-RRE-IIB complex formation could be due to desolvation and deionization of polar groups, which negatively compensates for the energy released due to hydrogen bond formation. As reported from molecular dynamics simulation studies [46] in case of Rev-RRE-IIB binding, water molecules involved in complex formation exhibit bulk water properties and screen the charge on the peptide and RNA backbone resulting in small enthalpic contribution for complex formation. On the other hand in case of RSG-1.2 bound water molecules make direct hydrogen bonds with peptide and with RNA bases which increases the enthalpic gain by forming a low energy RNA-water-peptide complex.…”

Section: Discussionmentioning

confidence: 89%

“…Furthermore these interactions are strong enough to compensate for unfavorable enthalpy associated with desolvation. Recent molecular dynamics simulation studies have shown that Rev makes a total of 26 hydrogen bonds and RSG-1.2 makes a total of 20 hydrogen bonds and a network of continuous salt bridges spanning the major groove [46]. Though the number of hydrogen bonds involved in Rev RRE-IIB complex formation is more than RSG-1.2-RRE-IIB complex, later one has a large negative enthalpy of binding ( ΔH = −13.9 kcal/mol) as compared to the negligible enthalpy of former one.…”

Section: Discussionmentioning

confidence: 99%

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Specificity of RSG-1.2 Peptide Binding to RRE-IIB RNA Element of HIV-1 over Rev Peptide Is Mainly Enthalpic in Origin

et al. 2011

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Rev is an essential HIV-1 regulatory protein which binds to the Rev responsive element (RRE) present within the env gene of HIV-1 RNA genome. This binding facilitates the transport of the RNA to the cytoplasm, which in turn triggers the switch between viral latency and active viral replication. Essential components of this complex have been localized to a minimal arginine rich Rev peptide and stem IIB region of RRE. A synthetic peptide known as RSG-1.2 binds with high binding affinity and specificity to the RRE-IIB than the Rev peptide, however the thermodynamic basis of this specificity has not yet been addressed. The present study aims to probe the thermodynamic origin of this specificity of RSG-1.2 over Rev Peptide for RRE-IIB. The temperature dependent melting studies show that RSG-1.2 binding stabilizes the RRE structure significantly (ΔT m = 4.3°C), in contrast to Rev binding. Interestingly the thermodynamic signatures of the binding have also been found to be different for both the peptides. At pH 7.5, RSG-1.2 binds RRE-IIB with a Ka = 16.2±0.6×107 M−1 where enthalpic change ΔH = −13.9±0.1 kcal/mol is the main driving force with limited unfavorable contribution from entropic change TΔS = −2.8±0.1 kcal/mol. A large part of ΔH may be due to specific stacking between U72 and Arg15. In contrast binding of Rev (Ka = 3.1±0.4×107 M−1) is driven mainly by entropy (ΔH = 0 kcal/mol and TΔS = 10.2±0.2 kcal/mol) which arises from major conformational changes in the RNA upon binding.

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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Specificity of RSG-1.2 Peptide Binding to RRE-IIB RNA Element of HIV-1 over Rev Peptide Is Mainly Enthalpic in Origin

et al. 2011

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“…Aromatic amino acids may, besides interaction through their polar heads, also interfere via their aromatic part of the molecule. The aromatic groups of these amino acids can be involved in non-covalent cation – π interactions with different cationic species [11, 14–17]. This kind of interaction in biological systems may play an important part, e.g., in biological recognition processes [17], selectivity and functioning of ion channels [18], or in drug-receptor interaction [19].…”

Section: Introductionmentioning

confidence: 99%

Effect of metal Ions (Ni2+, Cu2+ and Zn2+) and water coordination on the structure of L-phenylalanine, L-tyrosine, L-tryptophan and their zwitterionic forms

et al. 2011

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Methods of quantum chemistry have been applied to double-charged complexes involving the transition metals Ni2+, Cu2+ and Zn2+ with the aromatic amino acids (AAA) phenylalanine, tyrosine and tryptophan. The effect of hydration on the relative stability and geometry of the individual species studied has been evaluated within the supermolecule approach. The interaction enthalpies, entropies and Gibbs energies of nine complexes Phe•M, Tyr•M, Trp•M, (M = Ni2+, Cu2+ and Zn2+) were determined at the Becke3LYP density functional level of theory. Of the transition metals studied the bivalent copper cation forms the strongest complexes with AAAs. For Ni2+and Cu2+ the most stable species are the NO coordinated cations in the AAA metal complexes, Zn2+cation prefers a binding to the aromatic part of the AAA (complex II). Some complexes energetically unfavored in the gas-phase are stabilized upon microsolvation.

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“…This could arise because of the entrapment of water molecules around extra acetyl group leading to reduction of favorable entropic component. Entrapment of water molecule results in reduced enthalpic weightage to RNA binding [42] but as enthalpic component remained almost unaffected, we can speculate enthalpic component compensation by extra non-covalent interaction between, water and side chain of the amino acid and RNA. The comparison of the binding parameters at the second binding site shows a reduction, irrespective of the position of modification, in the binding affinity with favorable enthalpy-entropy compensation.…”

Section: Discussionmentioning

confidence: 93%

The Effect of N-acetylation and N-methylation of Lysine Residue of Tat Peptide on its Interaction with HIV-1 TAR RNA

Kumar

Maiti

2013

PLoS ONE

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Post-translational modification (PTM) of RNA binding proteins (RBPs) play a very important role in determining their binding to cognate RNAs and therefore regulate the downstream effects. Lysine can undergo various PTMs and thereby contribute to the regulation of different cellular processes. It can be reversibly acetylated and methylated using a pool of respective enzymes, to act as a switch for controlling the binding efficiency of RBPs. Here we have delineated the thermodynamic and kinetic effects of N-acetylation and N-monomethylation of lysine on interaction between HIV-1 TAR RNA and its cognate binder Tat peptide ( a model system). Our results indicate that acetylation of lysine 50 (K50), leads to eight- fold reduction in binding affinity, originating exclusively from entropy changes whereas, lysine 51 (K51) acetylation resulted only in three fold decrease with large enthalpy-entropy compensation. The measurement of kinetic parameters indicated major change (4.5 fold) in dissociation rate in case of K50 acetylation however, K51 acetylation showed similar effect on both association and dissociation rates. In contrast, lysine methylation did not affect the binding affinity of Tat peptide to TAR RNA at K50, nonetheless three fold enhancement in binding affinity was observed at K51 position. In spite of large enthalpy-entropy compensation, lysine methylation seems to have more pronounced position specific effect on the kinetic parameters. In case of K50 methylation, simultaneous increase was observed in the rate of association and dissociation leaving binding affinity unaffected. The increased binding affinity for methylated Tat at K51 stems from faster association rate with slightly slower dissociation rate.

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Water, Shape Recognition, Salt Bridges, and Cation–Pi Interactions Differentiate Peptide Recognition of the HIV Rev-Responsive Element

Cited by 17 publications

References 108 publications

Specificity of RSG-1.2 Peptide Binding to RRE-IIB RNA Element of HIV-1 over Rev Peptide Is Mainly Enthalpic in Origin

Specificity of RSG-1.2 Peptide Binding to RRE-IIB RNA Element of HIV-1 over Rev Peptide Is Mainly Enthalpic in Origin

Effect of metal Ions (Ni2+, Cu2+ and Zn2+) and water coordination on the structure of L-phenylalanine, L-tyrosine, L-tryptophan and their zwitterionic forms

The Effect of N-acetylation and N-methylation of Lysine Residue of Tat Peptide on its Interaction with HIV-1 TAR RNA

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