User:Benjamin Elliott/Crystal Structure of the Bromodomain-PHD Finger Module of Human Transcriptional Co-Activator CBP in complex with Acetylated Histone 4 Peptide (H4K20ac)

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 6: Line 6:
Bromodomains (BrDs) function exclusively as acetyl-lysine binding domains to regulate gene transcription in both histone and non-histone proteins<ref>DOI 10.1016/j.bbagrm.2014.03.011</ref>. This BrD of human transcriptional co-activator CBP binds with relatively high specificity to Lys20-acetylated histone H4 (H4K20), though this preference is not well-understood. The plant homeodomain (PHD) finger is hypothesized to play a structural role, since the entire module functions as one unit. It has been experimentally demonstrated that the module binds most effectively to singly acetylated peptide chains, with affinity significantly reduced with more acetylations. More specifically, it has been shown that the bromodomain prefers lysine-acetylated motifs comprising a hydrophobic or aromatic residue at -2 and a lysine or arginine at the -3 or -4 position<ref>DOI 10.1016/j.str.2013.10.021</ref>.
Bromodomains (BrDs) function exclusively as acetyl-lysine binding domains to regulate gene transcription in both histone and non-histone proteins<ref>DOI 10.1016/j.bbagrm.2014.03.011</ref>. This BrD of human transcriptional co-activator CBP binds with relatively high specificity to Lys20-acetylated histone H4 (H4K20), though this preference is not well-understood. The plant homeodomain (PHD) finger is hypothesized to play a structural role, since the entire module functions as one unit. It has been experimentally demonstrated that the module binds most effectively to singly acetylated peptide chains, with affinity significantly reduced with more acetylations. More specifically, it has been shown that the bromodomain prefers lysine-acetylated motifs comprising a hydrophobic or aromatic residue at -2 and a lysine or arginine at the -3 or -4 position<ref>DOI 10.1016/j.str.2013.10.021</ref>.
from the acetylated lysine.
from the acetylated lysine.
-
== Disease ==
+
 
 +
== Disease==
 +
In the larger complex, this domain functions as the domain that binds directly to the histone protein when it recognizes acetylation. Alterations in the of the human CBP gene results have been implicated in hematological malignancies as well as congenital malformation and mental retardation<ref> DOI 10.1016/S0168-9525(98)01438-3</ref>.
== Relevance ==
== Relevance ==
Line 13: Line 15:
This protein is composed of two different domains -- the bromodomain (BrD) and the plant homeodomain (PHD) finger. In this particular module for human CBP, the two come together to form such interactions that they function as a single structural unit.There are two <scene name='76/769329/Zinc_ions/1'>zinc ion coordination centers</scene> that serve as a stable base for an extended interface established between the PHD finger and the BrD. The PHD finger itself has not shown to bind any specific peptide, whether in tandem or in its individual construct <ref> DOI 10.1016/j.febslet.2013.06.051</ref>. The separation of the domains is shown <scene name='76/769329/Annoying_one/2'>here</scene>, with the BrD shown in aquamarine, the PHD finger shown in red, and the linkers of the two domains shown in blue.
This protein is composed of two different domains -- the bromodomain (BrD) and the plant homeodomain (PHD) finger. In this particular module for human CBP, the two come together to form such interactions that they function as a single structural unit.There are two <scene name='76/769329/Zinc_ions/1'>zinc ion coordination centers</scene> that serve as a stable base for an extended interface established between the PHD finger and the BrD. The PHD finger itself has not shown to bind any specific peptide, whether in tandem or in its individual construct <ref> DOI 10.1016/j.febslet.2013.06.051</ref>. The separation of the domains is shown <scene name='76/769329/Annoying_one/2'>here</scene>, with the BrD shown in aquamarine, the PHD finger shown in red, and the linkers of the two domains shown in blue.
-
There are two different sections which are missing electron density in their region, which suggests a high degree of structural mobility in solution. These regions are from <scene name='76/769329/1212-1253/1'>residue 1212 to 1253</scene> and <scene name='76/769329/Short_unshown_chain/1'>1261 to 1269</scene>. Though unshown in the crystal structure,
+
There are two different sections which are missing electron density in their region, which suggests a high degree of structural mobility in solution. These regions are from <scene name='76/769329/1212-1253/1'>residue 1212 to 1253</scene> and <scene name='76/769329/Short_unshown_chain/1'>1261 to 1269</scene>. Though unshown in the crystal structure, the lack of electron density associated with such a lack of imaging suggests a high degree of structural mobility through these sections.
This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.
This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

Revision as of 00:22, 10 October 2017

4N3W at Resolution 1.9 Å

Generic view of BrD-PHD finger module bound to H4K20ac

Drag the structure with the mouse to rotate

References

  1. ↑ Sanchez R, Meslamani J, Zhou MM. The bromodomain: from epigenome reader to druggable target. Biochim Biophys Acta. 2014 Aug;1839(8):676-85. doi: 10.1016/j.bbagrm.2014.03.011., Epub 2014 Mar 28. PMID:24686119 doi:http://dx.doi.org/10.1016/j.bbagrm.2014.03.011
  2. ↑ Plotnikov AN, Yang S, Zhou TJ, Rusinova E, Frasca A, Zhou MM. Structural Insights into Acetylated-Histone H4 Recognition by the Bromodomain-PHD Finger Module of Human Transcriptional Coactivator CBP. Structure. 2013 Dec 18. pii: S0969-2126(13)00437-1. doi:, 10.1016/j.str.2013.10.021. PMID:24361270 doi:http://dx.doi.org/10.1016/j.str.2013.10.021
  3. ↑ doi: https://dx.doi.org/10.1016/S0168-9525(98)01438-3
  4. ↑ Park S, Martinez-Yamout MA, Dyson HJ, Wright PE. The CH2 domain of CBP/p300 is a novel zinc finger. FEBS Lett. 2013 Aug 19;587(16):2506-11. doi: 10.1016/j.febslet.2013.06.051. Epub , 2013 Jul 4. PMID:23831576 doi:http://dx.doi.org/10.1016/j.febslet.2013.06.051

Proteopedia Page Contributors and Editors (what is this?)

Benjamin Elliott

Retrieved from "http://52.214.119.220/wiki/index.php/User:Benjamin_Elliott/Crystal_Structure_of_the_Bromodomain-PHD_Finger_Module_of_Human_Transcriptional_Co-Activator_CBP_in_complex_with_Acetylated_Histone_4_Peptide_%28H4K20ac%29"
Personal tools