Sandbox Reserved 490: Difference between revisions

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This is the structure of the estrogen receptor when its DNA binding domain is complexed to DNA. It binds as a <scene name='Sandbox_Reserved_490/Dbd_dimerization_domains/2'>symmetrical dimer</scene> to the appropriate DNA sequence. Each dimer consists of <scene name='Sandbox_Reserved_490/Dbd_secondary_structure/2'>two alpha helices and two antiparallel beta-sheets</scene>. The <scene name='Sandbox_Reserved_490/Dbd_active_residues/1'>active residues</scene> are located on the <scene name='Sandbox_Reserved_490/Dbd_hydrophobic/2'>hydrophilic</scene> face of the <scene name='Sandbox_Reserved_490/Dbd_recognition_helix/2'>recognition helix</scene>. These residues follow a modified zinc finger motif. The Glu-25, Lys-28, Lys-32, and Arg-33 residue side chains interact with the base pairs of the DNA. Other polar side chains less specifically with the phosphate backbone of the DNA.

This is the structure of the estrogen receptor when its DNA binding domain is complexed to DNA. It binds as a <scene name='Sandbox_Reserved_490/Dbd_dimerization_domains/2'>symmetrical dimer</scene> to the appropriate DNA sequence. Each dimer consists of <scene name='Sandbox_Reserved_490/Dbd_secondary_structure/2'>two alpha helices and two antiparallel beta-sheets</scene>. The <scene name='Sandbox_Reserved_490/Dbd_active_residues/1'>active residues</scene> are located on the <scene name='Sandbox_Reserved_490/Dbd_hydrophobic/2'>hydrophilic</scene> face of the <scene name='Sandbox_Reserved_490/Dbd_recognition_helix/2'>recognition helix</scene>. These residues follow a modified zinc finger motif. The Glu-25, Lys-28, Lys-32, and Arg-33 residue side chains interact with the base pairs of the DNA. Other polar side chains interact less specifically with the phosphate backbone of the DNA.

The DNA sequence that the dimerized estrogen receptor binds to is a palindromic sequence. This reflects the symmetric dimerization of the protein.

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==Mechanism of Action==

==Mechanism of Action<ref>PMID:17615392</ref>==

Two general mechanisms of action have been proposed for ER proteins: Genomic and non-genomic. Much of research has focused on the genomic mechanism of action, which is still not clearly understood.

''Genomic Mechanism''

== ~~Headline text~~ ==

The genomic mechanism of action occurs within the nucleus of the cell and can be either ligand-dependent or independent. The ligand-dependent mechanism requires the estrogen ligand to diffuse into the cell and then into the nucleus, bind to the LBD of the ER, and induce a conformational change in the receptor protein. The receptor protein then recruits specific co-factors and molecules and assembles a DNA-binding complex, which binds to specific DNA promoter or repressor sequences, depending on the type of cell.

Ligand-independent action of the ER occurs when some factor (for example, growth factor) induces a kinase cascade that ultimately phosphorylates the ER and induces the protein to dimerize and act upon DNA and gene transcription.

The ER may act as a transcription factor itself, or it may enhance the activity of other transcription factors. For example, ER has been shown to influence the activity of NFKb in transcribing interleukin-6. These genomic mechanisms are relatively slow.

''Non-Genomic Mechanism''

This mechanism is still largely undefined. However, it has been suggest that outside of the nucleus,

the occurrence of estrogen binding to ER may induce a rapid physiological change. However, it is unknown if this happens at the plasma membrane, withing the cytoplasm, or through the action of an unknown intermediary protein.

The following image summarizes the action mechanisms of ER:

[[Image:Example.jpg]]

== Clinical Applications ==

Discovering the mechanisms by which ER acts to regulate gene expression has had, and will continue to have, consequences for the way we treat diseases in tissues that

== References ==

Sandbox Reserved 490: Difference between revisions

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@@ Line 26: / Line 26: @@
 <Structure load='1hcq' size='300' frame='true' align='right' caption='ER DBD' scene='' />
-This is the structure of the estrogen receptor when its DNA binding domain is complexed to DNA. It binds as a <scene name='Sandbox_Reserved_490/Dbd_dimerization_domains/2'>symmetrical dimer</scene> to the appropriate DNA sequence. Each dimer consists of <scene name='Sandbox_Reserved_490/Dbd_secondary_structure/2'>two alpha helices and two antiparallel beta-sheets</scene>. The <scene name='Sandbox_Reserved_490/Dbd_active_residues/1'>active residues</scene> are located on the <scene name='Sandbox_Reserved_490/Dbd_hydrophobic/2'>hydrophilic</scene> face of the <scene name='Sandbox_Reserved_490/Dbd_recognition_helix/2'>recognition helix</scene>. These residues follow a modified zinc finger motif. The Glu-25, Lys-28, Lys-32, and Arg-33 residue side chains interact with the base pairs of the DNA. Other polar side chains less specifically with the phosphate backbone of the DNA.
+This is the structure of the estrogen receptor when its DNA binding domain is complexed to DNA. It binds as a <scene name='Sandbox_Reserved_490/Dbd_dimerization_domains/2'>symmetrical dimer</scene> to the appropriate DNA sequence. Each dimer consists of <scene name='Sandbox_Reserved_490/Dbd_secondary_structure/2'>two alpha helices and two antiparallel beta-sheets</scene>. The <scene name='Sandbox_Reserved_490/Dbd_active_residues/1'>active residues</scene> are located on the <scene name='Sandbox_Reserved_490/Dbd_hydrophobic/2'>hydrophilic</scene> face of the <scene name='Sandbox_Reserved_490/Dbd_recognition_helix/2'>recognition helix</scene>. These residues follow a modified zinc finger motif. The Glu-25, Lys-28, Lys-32, and Arg-33 residue side chains interact with the base pairs of the DNA. Other polar side chains interact less specifically with the phosphate backbone of the DNA.
 The DNA sequence that the dimerized estrogen receptor binds to is a palindromic sequence. This reflects the symmetric dimerization of the protein.
@@ Line 68: / Line 68: @@
-==Mechanism of Action==
+==Mechanism of Action<ref>PMID:17615392</ref>==
 Two general mechanisms of action have been proposed for ER proteins: Genomic and non-genomic. Much of research has focused on the genomic mechanism of action, which is still not clearly understood.
+''Genomic Mechanism''
-== Headline text ==
+The genomic mechanism of action occurs within the nucleus of the cell and can be either ligand-dependent or independent. The ligand-dependent mechanism requires the estrogen ligand to diffuse into the cell and then into the nucleus, bind to the LBD of the ER, and induce a conformational change in the receptor protein. The receptor protein then recruits specific co-factors  and molecules and assembles a DNA-binding complex, which binds to specific DNA promoter or repressor sequences, depending on the type of cell.
+Ligand-independent action of the ER occurs when some factor (for example, growth factor) induces a kinase cascade that ultimately phosphorylates the ER and induces the protein to dimerize and act upon DNA and gene transcription.
+The ER may act as a transcription factor itself, or it may enhance the activity of other transcription factors. For example, ER has been shown to influence the activity of NFKb in transcribing interleukin-6. These genomic mechanisms are relatively slow.
+''Non-Genomic Mechanism''
+This mechanism is still largely undefined. However, it has been suggest that outside of the nucleus,
+the occurrence of estrogen binding to ER may induce a rapid physiological change. However, it is unknown if this happens at the plasma membrane, withing the cytoplasm, or through the action of an unknown intermediary protein.
+The following image summarizes the action mechanisms of ER:
+[[Image:Example.jpg]]
+== Clinical Applications ==
+Discovering the mechanisms by which ER acts to regulate gene expression has had, and will continue to have, consequences for the way we treat diseases in tissues that
 == References ==
 <references />