Alleles of the MC1R Gene in the Grey Squirrel

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ABSTRACT

We analyzed structural features of 11,038 direct atomic contacts (either electrostatic, H-bonds, hydrophobic, or other van der Waals interactions) extracted from 139 protein-DNA and 49 protein-RNA nonhomologous complexes from the Protein Data Bank (PDB). Globally, H-bonds are the most frequent interactions (~50%), followed by van der Waals, hydrophobic, and electrostatic interactions. From the protein viewpoint, hydrophilic amino acids are over-represented in the interaction databases: Positively charged amino acids mainly contact nucleic acid phosphate groups but can also interact with base edges. From the nucleotide point of view, DNA and RNA behave differently: Most protein-DNA interactions involve phosphate atoms, while protein-RNA interactions involve more frequently base edge and ribose atoms. The increased participation of DNA phosphate involves H-bonds rather than salt bridges. A statistical analysis was performed to find the occurrence of amino acid-nucleotide pairs most different from chance. These pairs were analyzed individually. Finally, we studied the conformation of DNA in the interaction sites. Despite the prevalence of B-DNA in the database, our results suggest that A-DNA is favored in the interaction sites

Alleles of the MC1R Gene in the Grey Squirrel

Introduction

Interactions between proteins and other biological molecules, especially nucleic acids, are the basis of cell life. DNA-binding proteins are coded by 2-3% of the genome in prokaryotes, and 6-7% in eukaryotes. These nucleic acid-binding proteins are involved in fundamental roles as replication, transcription, restriction, and even viral infection.

The recognition of a specific nucleotide sequence by a DNA- or RNA-binding protein is determined by atomic interactions between amino acids and nucleotides. Attempts to determine the rules of this recognition began in the 1970s.2 Of all possible types of interactions, hydrogen bonds between amino acids and base edges were shown to be the most relevant. Most H-bonds involve protein side-chains and contribute to the protein specificity, while interactions between nucleotides and protein backbone seem to be important for the stabilization and orientation of the complex (Cheung, 2005, pp.4601-4611). The specificity due to side-chain H-bonds cannot be explained in terms of a one-to-one mechanism, but rather in terms of a one-to-many interaction, such as bidentate or bifurcated H-bonds, and complex H-bonds contacting several base steps.

In addition to the well-recognized H-bonds (NHO, OHO), at least two other types of H-bonds have been shown to be involved in protein-nucleic acid interaction. First, the CHO interactions have been shown to frequently link the CH groups in the DNA major groove and protein side-chain oxygens. The same CHO bonds make up 33% of the H-bonds between protein and RNA. Second, water-mediated H-bonds account for 15% of all protein-DNA interactions and are involved in minimizing the electrostatic repulsion of aspartate and glutamate from DNA phosphates. Such interactions are surprisingly frequent in protein-RNA contacts.

Ionic interactions between positively charged amino acids and phosphate oxygen are important for stabilizing complexesand could be involved in the long-distance preorientation of peptidic chains. In addition, some DNA-binding proteins bend nucleotide chains, modifying the mechanism of DNA recognition by amino acids. The ability of DNA to bend appears ...