Specific protein–DNA interactions underlie binding

As we have seen, transcription factors with specific DNA-binding domains are involved in the activation and inactivation of specific genes. There are several common structural themes in the *protein domains that bind to DNA. These themes, or structural motifs, consist of different combinations of structural elements (protein conformations) and may include special components such as zinc. One of the common structural motifs is the helix-turn-helix, in which two α helices are connected via a non-helical turn. The interior-facing “recognition” helix interacts with the bases inside the DNA. The exterior-facing helix sits on the sugar–phosphate backbone, ensuring that the interior helix is presented to the bases in the correct configuration:

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*connect the concepts The structure and chemistry of DNA are key to its recognition by proteins. How the shapes and chemical structures of proteins allow them to bind noncovalently to other molecules is covered in Key Concept 3.2.

How does a protein recognize a sequence in DNA? As you learned in Key Concept 3.2, the complementary bases in DNA not only form hydrogen bonds with each other, but also can form additional hydrogen bonds with proteins, particularly at points exposed in the major and minor grooves. In this way, an intact DNA double helix can be recognized by a protein motif whose structure: