Structural Biochemistry/Protein-DNA Recognition

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Protein-DNA Recognition[edit | edit source]

The binding affinity of DNA was traditionally thought to be dictated by its surrounding bases and phosphates. However, recent discoveries have shed light upon the role that interactions between DNA and selective residues, which were previously thought to be outside of the binding interface, affect genetic expression. When these regions bind to DNA, they do not result in a fixed structure. Rather, they create a dynamic complex which serves to regulate the transcription of RNA from DNA. This includes regulation of not only the machinery used to make RNA but also modifications to the pre-mRNA. [1]

Basic Mechanisms of Protein-DNA interaction[edit | edit source]

The process whereby DNA is transcribed into RNA and RNA is translated into a protein in its simplest form was thought to be controlled by characteristic indirect and direct mechanisms. These mechanisms are generally understood in terms of hydrogen bonding and electrostatic interactions. Hydrogen bonding between corresponding bases serves as a direct DNA template. The structure of DNA is also indirectly influenced by interactions between phosphate groups.[1]

Delving further into DNA Readout[edit | edit source]

Looking beyond the basic mechanisms which influence DNA conformation, we must also consider a plethora of other factors that determine how DNA can change its shape and flexibility during transcription. One of the primary factors that helps determine the geometry of a DNA molecule is its groove and width. The electrostatic potential of the molecule, primarily its ability to bind to proteins, is dictated by the geometry of the complex. Proteins that bind to DNA are fitted with segments which recognize specific DNA sequences. These segments are referred to as ID segments because they are intrinsically disordered and they can distinguish and bind to DNA at multiple stages. Although the mechanism by which ID segments influence the shape of DNA is not fully understood, it is theorized that ID segments work much like other globular proteins and fold into a designated shape once they make contact with their target sequence on the DNA. One of the most important roles of ID segments is guiding DNA-binding proteins along a complex. ID segments also help a DNA complex transition into a more specific state. [1]

ID Segments in Protein-Protein Interactions[edit | edit source]

The function of ID segments has been best studied in protein-protein interactions. In these interactions, ID regions initially appear to serve no distinguishing purpose. However, upon closer inspection, it is clear that ID regions influence both binding affinity and selectivity between proteins. ID regions can change the binding affinity between two proteins by adopting different conformations which allows for different binding interactions and more mobility. [1]

ID segments in Protein-DNA Interactions[edit | edit source]

Although the role of ID segments in DNA-protein interactions is not as well understood as the role of ID segments in protein-protein interactions, researchers do know that in most DNA-protein interactions for eukaryotic cells transcription factors only target the DNA binding region of the protein. This may be because ID regions tend to be more susceptible to degradation by proteolysis. Roughly 70% of proteins that bind DNA contain ID regions, which are usually localized on the tail. These ID segments give the tail a charge which functions in the identification of DNA sequences using electrostatic interactions. Electrostatic DNA-protein interactions are nonspecific, and they minimize the presence of free DNA-binding proteins. [2]