While DNA contains all the genetic material in a cell, proteins play an important role in regulating the transcription of DNA to RNA, not to mention replication, repair and packaging.. The interactions between DNA and proteins are important in this process. Most sequence specific interactions occur in the major grove, as the bases are exposed in this groove. In contrast, the minor grove contains more of the carbohydrate portions of DNA.
Helix-Turn-Helix Interactions with DNAThe first DNA binding domain characterized was the helix-turn-helix. In a helix-turn-helix protein such as the Cro repressor, two α helices are joined by a turn; there may be additional supporting structures, such as additional helices or beta strands, but this is the basic motif. In most cases, the C terminal helix contributes most to DNA recognition, and hence it is often called the "recognition helix". It binds to the major groove of DNA through a series of hydrogen bonds and various Van der Waals interactions with exposed bases. For example, Asn51 forms hydrogen bonds with both A219 and A220 of the DNA strand. There are also ionic interactions between basic protein residues, such as Lys and Arg, with the backbone phosphate groups. The N-terminal alpha helix stabilizes the interaction between the interaction between protein and DNA, but does not play a particularly strong role in its recognition.[2] The recognition helix and its preceding helix always have the same relative orientation.[ Leucine zippersThe Basic Leucine Zipper Domain (bZIP domain) is found in many DNA binding eukaryotic proteins, especially transcription factors such as the cAMP Responsive Element Binding (CREB) protein . One part of the domain contains a region that mediates sequence specific DNA binding properties via basic amino acids such as arginine and lysine. These basic residues can either interact ionically with the negatively charged backbone phosphate groups or via hydrogen bonds with the bases. Since these basic amino acids would usually repel, the leucine zipper segment allows for dimerization of the protein. Notice the spacing of the leucine residues; they are spaced by 3, 4, or 7 amino acids, causing them to be on the same face of the alpha helix. this hydrophobic set of "zipper teeth" allows this region to interact with another monomer unit, pairing with the exact same residues to form a hydrophobic core, shown in grey. At the base of the leucine zipper, where the protein meets the DNA, is positioned a magnesium ion. While you would expect a divalent cation to be surrounded by negatively charged amino acids from the protein or backbone phosphates from the DNA, its inner chelation sphere is completely composed of water molecules. The next sphere of interactions include two lysine residues (one from each protein chain) Zinc fingersGAL4 is a transcription factor that induces genes required for the metabolism of galactose, specifically enzymes involved in the conversion of galactose to glucose, and is an example of a zinc finger DNA binding protein. The protein binds as a dimer to a symmetrical 17-base-pair sequence. Each subunit folds into three distinct modules: a compact, metal binding domain(residues 8-40), an extended linker(41-49), and an alpha-helical dimerization element (50-64). The small, Zn(2+)-containing domain, which contains two metal ions tetrahedrally coordinated by six cysteines. This metal binding domain recognizes a conserved CCG triplet at each end of the site through direct contacts with the major groove, including hydrogen bonding between a lysine and the conserved G. A short coiled-coil dimerization element imposes 2-fold symmetry. A segment of extended polypeptide chain links the metal-binding module to the dimerization element and specifies the length of the site. The relatively open structure of the complex would allow another protein to bind coordinately with GAL4.
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This page was last modified 16:15, 17 March 2016.