A binding mechanism in protein-nucleotide interactions: implication for U1A RNA binding.
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.
Guallar
Victor
V
Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63108, USA. guallarv@biochem.wustl.edu
Borrelli
Kenneth W
KW
D000465:Algorithms; D020816:Amino Acid Motifs; D001224:Aspartic Acid / Q000378:metabolism; D008958:Models, Molecular; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary; D012313:RNA / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D017412:Ribonucleoprotein, U1 Small Nuclear / Q000378:metabolism*
D016601:RNA-Binding Proteins; D017412:Ribonucleoprotein, U1 Small Nuclear; C075339:U1A protein; D001224:Aspartic Acid; D012313:RNA