A binding mechanism in protein-nucleotide interactions: implication for U1A RNA binding.

Victor Guallar; Kenneth W Borrelli

doi:10.1073/pnas.0500888102

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A binding mechanism in protein-nucleotide interactions: implication for U1A RNA binding.

Victor Guallar·Kenneth W Borrelli

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Abstract

We present a close electronic view of the protein-base interface for the N-terminal domain of the human protein U1A. Combining accurate mixed quantum mechanics/molecular mechanics techniques and protein structure prediction methods, we provide a detailed electronic structure description of the protein-RNA stacking interactions. Our analysis indicates the evolution of the protein structure optimizing the interaction between Asp-92 and the RNA bases. The results show a direct coupling of the C-terminal tail and Asp-92, providing a direct rationalization of the experimentally determined role of the C-terminal domain in RNA binding. Here, we propose a mechanism where a protein side chain, with a delocalized electronic pi system, assists in the nucleotide binding. The binding mechanism involves a short-range interaction of the side chain with the nucleotide base and an electronic long-range interaction through a sandwich-stacking motif. The structural motif of the binding mechanism is observed in similar protein-RNA interactions and in various protein-ATP-binding sites.

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Algorithms Amino Acid Motifs Aspartic Acid Models, Molecular Protein Binding Protein Structure, Tertiary RNA RNA-Binding Proteins Ribonucleoprotein, U1 Small Nuclear Journal Article Research Support, Non-U.S. Gov't

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Victor Guallar, Kenneth W Borrelli. 2005-03-07. A binding mechanism in protein-nucleotide interactions: implication for U1A RNA binding.. https://doi.org/10.1073/pnas.0500888102

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