DNA-protein interactions: Difference between revisions
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==DNA-Protein interactions== | ==DNA-Protein interactions== | ||
<StructureSection load='1d66' size='340' side='right' caption='Gal4 transcriptional activator interacting with its target DNA | <StructureSection load='1d66' size='340' side='right' caption='Gal4 transcriptional activator interacting with its target DNA (PDB code [[1d66]])'> | ||
__TOC__ | |||
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 <scene name='71/711660/Grooves/1'>major grove</scene>, as the <scene name='71/711660/Base_exposure/1'>bases are exposed</scene> in this groove. In contrast, the <scene name='71/711660/Grooves/1'>minor grove</scene> contains more of the <scene name='71/711660/Base_exposure/1'>carbohydrate portions</scene> of DNA. | 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 <scene name='71/711660/Grooves/1'>major grove</scene>, as the <scene name='71/711660/Base_exposure/1'>bases are exposed</scene> in this groove. In contrast, the <scene name='71/711660/Grooves/1'>minor grove</scene> contains more of the <scene name='71/711660/Base_exposure/1'>carbohydrate portions</scene> of DNA. | ||
== Helix-Turn-Helix Interactions with DNA== | == Helix-Turn-Helix Interactions with DNA== | ||
The first DNA binding domain characterized was the helix-turn-helix. In a <scene name='71/711660/Protein_rainbow/1'>helix-turn-helix protein</scene> 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 <scene name='71/711660/C_terminal_helix/1'>C terminal helix</scene> 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, <scene name='71/711660/Asn51_da219_a220/1'>Asn51</scene> forms hydrogen bonds with both A219 and A220 of the DNA strand. | The first DNA binding domain characterized was the helix-turn-helix. In a <scene name='71/711660/Protein_rainbow/1'>helix-turn-helix protein</scene> 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 <scene name='71/711660/C_terminal_helix/1'>C terminal helix</scene> 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, <scene name='71/711660/Asn51_da219_a220/1'>Asn51</scene> forms hydrogen bonds with both A219 and A220 of the DNA strand. There are also ionic interactions between basic protein residues, such as <scene name='71/711660/Ionic_interactions/1'> Lys and Arg</scene>, 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 zippers == | == Leucine zippers == | ||
The Basic Leucine Zipper Domain (<scene name='71/711660/Creb/1'>bZIP domain</scene>) 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 <scene name='71/711660/Creb_charge/2'>basic amino acids</scene> such as arginine and lysine. These basic residues can either interact ionically with the <scene name='71/711660/Creb_arg_p/1'>negatively charged backbone phosphate groups</scene> or via <scene name='71/711660/Creb_arg_hbond/1'>hydrogen bonds</scene> with the bases. | |||
Since these basic amino acids would usually repel, the <scene name='71/711660/Creb_leu/1'>leucine zipper segment</scene> 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 <scene name='71/711660/Creb_hydrophobic/1'>hydrophobic core</scene>, shown in grey. At the base of the leucine zipper, where the protein meets the DNA, is positioned a <scene name='71/711660/Creb__mg/1'>magnesium ion</scene>. 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 <scene name='71/711660/Creb_h2o_mg/1'>water molecules</scene>. The next sphere of interactions include <scene name='71/711660/Creb_lys304/1'>two lysine residues</scene> (one from each protein chain) | |||
== Zinc fingers == | == Zinc fingers == | ||
<scene name='71/711660/Gal4/1'>GAL4</scene> 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 <scene name='Taylor_Gal4_Sandbox/Dimer/1'>dimer</scene> to a symmetrical 17-base-pair sequence. Each subunit folds into three distinct modules: a compact, <scene name='Taylor_Gal4_Sandbox/Metal_binding_domain/2'>metal binding domain</scene>(residues 8-40), an extended <scene name='Taylor_Gal4_Sandbox/Linker/1'>linker</scene>(41-49), and an <scene name='Taylor_Gal4_Sandbox/Dimerization/1'>alpha-helical dimerization element</scene> (50-64). The small, <scene name='Taylor_Gal4_Sandbox/Zn_binding/1'>Zn(2+)-containing domain</scene>, which contains two metal ions tetrahedrally coordinated by six cysteines. This metal binding domain recognizes a conserved <scene name='71/711660/Ccg/1'>CCG triplet</scene> at each end of the site through direct contacts with the <scene name='Taylor_Gal4_Sandbox/Major_groove/1'>major groove</scene>, including hydrogen bonding between a <scene name='71/711660/Gal_4_lys_to_g/1'>lysine and the conserved G</scene>. 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. | |||
</StructureSection> | </StructureSection> | ||
==See Also== | |||
*[[Lac repressor]] which explains specific and non-specific binding of the repressor protein to DNA, animates the transition between these kinds of binding (a [[Morphs|morph]]), how proteins recognize specific sequences in the major and minor grooves, and the differences between bends and kinks in DNA. | |||
== References == | == References == | ||
<references/> | <references/> | ||