Ku protein: Difference between revisions
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. This contributes to genomic integrity through its ability to bind DNA double-strand breaks and facilitate repair by the non-homologous end-joining pathway. The crystal structure of the human Ku heterodimer was determined both alone and | . This contributes to genomic integrity through its ability to bind DNA double-strand breaks and facilitate repair by the non-homologous end-joining pathway. The crystal structure of the human Ku heterodimer was determined both alone and | ||
<scene name='56/567269/Bound_dna/3'>bound to a 55-nucleotide DNA</scene> | <scene name='56/567269/Bound_dna/3'>bound to a 55-nucleotide DNA</scene> | ||
element at 2.7 and 2.5 A resolution, respectively. Ku70 and Ku80 share a common topology and form a dyad-symmetrical molecule with a preformed ring that encircles duplex DNA. The binding site can cradle two full turns of DNA while encircling only the central 3-4 base pairs (bp). Ku makes no contacts with DNA bases and few with the sugar-phosphate backbone, but it fits sterically to major and minor groove contours so as to position the DNA helix in a defined path through the protein ring. These features seem well designed to structurally support broken DNA ends and to bring the DNA helix into phase across the junction during end processing and ligation. <ref name=" | element at 2.7 and 2.5 A resolution, respectively. Ku70 and Ku80 share a common topology and form a dyad-symmetrical molecule with a preformed ring that encircles duplex DNA. The binding site can cradle two full turns of DNA while encircling only the central 3-4 base pairs (bp). Ku makes no contacts with DNA bases and few with the sugar-phosphate backbone, but it fits sterically to major and minor groove contours so as to position the DNA helix in a defined path through the protein ring. These features seem well designed to structurally support broken DNA ends and to bring the DNA helix into phase across the junction during end processing and ligation. <ref name="Walker"> PMID: 11493912</ref> | ||
[[Image:1jeq.jpg|350px|center|thumb| Crystal structure of Ku Heterodimer unbound to DNA<ref | [[Image:1jeq.jpg|350px|center|thumb| Crystal structure of Ku Heterodimer unbound to DNA<ref name="Walker"/>]] | ||
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=== Ku Ring === | === Ku Ring === | ||
The <scene name='56/567269/Ku_ring/1'>Ku Ring</scene> is composed of a broad base of beta barrels that cradle the DNA, and a narrow bridge that serves to protect the double strand break from base pairing with other DNA base pairs and degradation <ref name=" | The <scene name='56/567269/Ku_ring/1'>Ku Ring</scene> is composed of a broad base of beta barrels that cradle the DNA, and a narrow bridge that serves to protect the double strand break from base pairing with other DNA base pairs and degradation <ref name="Walker"/>. There is little interaction between the ring and the backbone or base pairs of DNA; instead, the ring associates with DNA by the cradle fitting into the major grooves of the helix <ref name="Walker"/>. The positive electrostatic charge caused by polarization of the ring also allows the negatively charged backbone of DNA to be guided into the correct position <ref name="Walker"/> (NEED SCENE OF POS CHARGE OR POLARIZATION). The Ku protein also has a high affinity to DNA due to its form being preset for the helix. As a result of the asymmetric ring, there is a strong preference (Kd value of 1.5 to 4 X 10^-10 M<ref> PMID: 11493912</ref>) for the <scene name='56/567269/Ku_ring/1'>Ku Ring</scene> to slide onto the ends of DNA <ref name="1"/>. In addition, other asymmetric features, such as a abundance of Asp residues on the N terminus of the <scene name='56/567269/Ku_heterodimer/3'>Ku heterodimer</scene> (NEED SCENE OF ASP ON N-TERMINUS OR MAYBE JUST ASP IN GENERAL), prevent the Ku protein from sliding further on the DNA helix. While wrapping over the entire helix, the <scene name='56/567269/Ku_ring/1'>Ku Ring</scene> is thin over the bridge, allowing ligases and polymerases to efficiently interact in [[non-homologous end joining (NHEJ)]]. <ref name="Walker"/> | ||
== Domains == | == Domains == | ||