Peroxisome Proliferator-Activated Receptors: Difference between revisions
David Canner (talk | contribs) No edit summary |
David Canner (talk | contribs) No edit summary |
||
| Line 2: | Line 2: | ||
{{STRUCTURE_3dzy| right| PDB=3dzy | SCENE=Peroxisome_Proliferator-Activated_Receptors/Ppar_opening4/1 |CAPTION= Crystal Structure of Human PPARγ, [[3dzy]] }} | {{STRUCTURE_3dzy| right| PDB=3dzy | SCENE=Peroxisome_Proliferator-Activated_Receptors/Ppar_opening4/1 |CAPTION= Crystal Structure of Human PPARγ, [[3dzy]] }} | ||
The [[Peroxisome Proliferator-Activated Receptors]] (PPAR) α, δ, and γ are members of the nuclear receptor family. Since their discovery in the early 90s, it has become clear that the PPARs are essential modulators of external stimuli, acting as transcription factors to regulate mammalian metabolism, cellular differentiation, and tumorigenesis. The PPARs are the targets of numerous pharmaceutical drugs aimed at treating hypolipidemia and [[diabetes]] among other diseases.<ref name="Berger"/> | The [[Peroxisome Proliferator-Activated Receptors]] (PPAR) α, δ, and γ are members of the nuclear receptor family. Since their discovery in the early 90s, it has become clear that the PPARs are essential modulators of external stimuli, acting as transcription factors to regulate mammalian metabolism, cellular differentiation, and tumorigenesis. The PPARs are the targets of numerous pharmaceutical drugs aimed at treating hypolipidemia and [[diabetes]] among other diseases.<ref name="Berger"/> | ||
{{TOC limit|limit=2}} | {{TOC limit|limit=2}} | ||
==Biological Role== | ==Biological Role== | ||
[[Image: PPAR_Mechanism.png|400px|left|thumb| PPAR Mechanism of Action in the Human Body]] | [[Image: PPAR_Mechanism.png|400px|left|thumb| PPAR Mechanism of Action in the Human Body]] | ||
| Line 32: | Line 30: | ||
When PPAR is bound to a co-repressor, the <scene name='Peroxisome_Proliferator-Activated_Receptors/H12_in_alpha/4'>hydrogen bond between Tyr 464 in PPAR alpha in AF-2 and other AF-2 stabilizing helices is destroyed</scene>, preventing the AF-2 H12 helix from occupying its active state. This in turn eliminates the charge clamp between PPAR and a prospective co-activator.<ref name="Gampe"/> Notice the <scene name='Peroxisome_Proliferator-Activated_Receptors/H12_in_alpha_active/2'>position of H12 when bound to a co-activator.</scene> | When PPAR is bound to a co-repressor, the <scene name='Peroxisome_Proliferator-Activated_Receptors/H12_in_alpha/4'>hydrogen bond between Tyr 464 in PPAR alpha in AF-2 and other AF-2 stabilizing helices is destroyed</scene>, preventing the AF-2 H12 helix from occupying its active state. This in turn eliminates the charge clamp between PPAR and a prospective co-activator.<ref name="Gampe"/> Notice the <scene name='Peroxisome_Proliferator-Activated_Receptors/H12_in_alpha_active/2'>position of H12 when bound to a co-activator.</scene> | ||
===Formation of Heterodimer with RXR=== | ===Formation of Heterodimer with RXR=== | ||
The interface of PPAR and RXR is composed of an intricate <scene name='Peroxisome_Proliferator-Activated_Receptors/Dimer_interface/1'>network of hydrophobic </scene>and <scene name='Peroxisome_Proliferator-Activated_Receptors/Dimer_interface_polar/2'>polar interactions </scene>which show remarkable complementarity. For the PPARγ-RXRα dimer the dimmer interface interactions are particularly extensive. <ref name="Gampe"/> | The interface of PPAR and RXR is composed of an intricate <scene name='Peroxisome_Proliferator-Activated_Receptors/Dimer_interface/1'>network of hydrophobic </scene>and <scene name='Peroxisome_Proliferator-Activated_Receptors/Dimer_interface_polar/2'>polar interactions </scene>which show remarkable complementarity. For the PPARγ-RXRα dimer the dimmer interface interactions are particularly extensive. <ref name="Gampe"/> | ||
===DNA Binding Domain Structure=== | ===DNA Binding Domain Structure=== | ||