JMS/Sandbox/msn2
From Proteopedia
(Difference between revisions)
(Replacing page with '# Msn2 (P33748): Interactive Structure of a Yeast Stress-Responsive Transcription Factor <applet load='AF-P33748-F1-model v4.pdb' size='400' frame='true' align='right' caption...') |
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<applet load='AF-P33748-F1-model v4.pdb' size='400' frame='true' align='right' caption='' scene='10/1080095/Msn2/1'/>__NOTOC__ | <applet load='AF-P33748-F1-model v4.pdb' size='400' frame='true' align='right' caption='' scene='10/1080095/Msn2/1'/>__NOTOC__ | ||
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- | ## Introduction | ||
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- | Msn2 (UniProt P33748) is a key transcription factor in *Saccharomyces cerevisiae* (baker's yeast) that orchestrates the general stress response (GSR).[1, 2] Along with its paralog Msn4, it binds to Stress Response Elements (STREs) in the promoters of numerous genes involved in protecting the cell against diverse environmental challenges like heat shock, osmotic stress, and nutrient limitation.[3, 2] Msn2's activity is primarily regulated by its dynamic localization between the cytoplasm and the nucleus, a process controlled by phosphorylation, notably by Protein Kinase A (PKA).[2, 4] | ||
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- | This page utilizes the AlphaFold structural prediction for Msn2 [5, 6] and interactive Jmol scripting to explore key functional domains and regulatory sites. | ||
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- | ## Interactive Exploration | ||
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- | Use the links below to highlight specific features on the 3D model to the right. The default view colors the structure by AlphaFold's prediction confidence (pLDDT score), ranging from very low confidence (red) through low (yellow) and confident (green) to very high confidence (blue).[5] | ||
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- | (<jmol><jmolLink> | ||
- | <script> | ||
- | # Reset and set base view (Grey cartoon + pLDDT colored wireframe atoms) | ||
- | select all; | ||
- | cartoon on; color cartoon grey; | ||
- | wireframe 0.1; spacefill off; | ||
- | color atoms property bfactor range 0 100; | ||
- | color atoms property_bfactor >= 90 "#084594"; # Very High (>90) - Blue | ||
- | color atoms property_bfactor < 90 and property_bfactor >= 70 "#20BF55"; # Confident (70-90) - Green | ||
- | color atoms property_bfactor < 70 and property_bfactor >= 50 "#F9D142"; # Low (50-70) - Yellow | ||
- | color atoms property_bfactor < 50 "#E60A0A"; # Very Low (<50) - Red | ||
- | selectionHalos OFF; backbone 0.5; # Set default backbone thickness | ||
- | center protein; zoom 100; | ||
- | </script> | ||
- | <text>Reset View (Color by pLDDT Confidence)</text> | ||
- | </jmolLink></jmol>) | ||
- | |||
- | (<jmol><jmolLink> | ||
- | <script> | ||
- | # Reset and set base view (Grey cartoon + pLDDT colored wireframe atoms) | ||
- | select all; | ||
- | cartoon on; color cartoon grey; | ||
- | wireframe 0.1; spacefill off; | ||
- | color atoms property bfactor range 0 100; | ||
- | color atoms property_bfactor >= 90 "#084594"; # Very High (>90) - Blue | ||
- | color atoms property_bfactor < 90 and property_bfactor >= 70 "#20BF55"; # Confident (70-90) - Green | ||
- | color atoms property_bfactor < 70 and property_bfactor >= 50 "#F9D142"; # Low (50-70) - Yellow | ||
- | color atoms property_bfactor < 50 "#E60A0A"; # Very Low (<50) - Red | ||
- | selectionHalos OFF; backbone 0.5; # Set default backbone thickness | ||
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- | # Highlight regions by backbone color | ||
- | select 647-675, 676-703; color backbone magenta; backbone 0.7; # Zinc Fingers [5] | ||
- | select 567-648; color backbone cyan; backbone 0.6; # NLS [4] | ||
- | select 283-293; color backbone orange; backbone 0.6; # NES Region [4] | ||
- | select 261-269; color backbone lime; backbone 0.6; # 9aaTAD [1] | ||
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- | # Highlight specific atoms | ||
- | select zn; spacefill 1.2; color cpk; # Zinc ions | ||
- | select 288, 582, 620, 625, 633; color atoms yellow; spacefill 100%; # PKA Sites [7, 4] | ||
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- | # Final view adjustments | ||
- | center protein; zoom 100; | ||
- | </script> | ||
- | <text>Show All Highlighted Features Simultaneously</text> | ||
- | </jmolLink></jmol>) | ||
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- | {{Clear}} | ||
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- | ### C2H2 Zinc Finger Domains (DNA Binding) | ||
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- | Msn2 binds DNA via two classical C2H2 zinc finger domains located near the C-terminus.[1, 2] UniProt annotation places these at approximately residues 647-675 and 676-703.[8] These domains recognize the Stress Response Element (STRE) sequence (5'-CCCCT-3') in the promoters of target genes.[3, 2] Recent studies suggest they may also bind G-quadruplex (G4) DNA structures.[9, 10] The AlphaFold model predicts these C-terminal domains with very high confidence (blue regions in the default view), consistent with a stable structure required for DNA interaction.[5, 6] Click the link to highlight these domains (residues 647-665 and 676-698 used for visualization) and the coordinating Zinc ions. | ||
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- | (<jmol><jmolLink> | ||
- | <script> | ||
- | select 647-665, 676-698; color magenta; backbone 0.7; wireframe 0.15; | ||
- | select zn; spacefill 1.2; color cpk; | ||
- | selectionHalos ON; delay 1.5; selectionHalos OFF; | ||
- | center selected; zoom 150; | ||
- | </script> | ||
- | <text>Highlight Zinc Fingers (DNA Binding: 647-665, 676-698)</text> | ||
- | </jmolLink></jmol>) | ||
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- | ### 9aaTAD Transactivation Motif | ||
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- | Located within the largely disordered N-terminal region is a conserved 9-amino-acid transactivation domain (9aaTAD) motif (residues 261-269).[1] This motif is common in yeast transcription factors and is crucial for recruiting the transcriptional machinery, potentially via interaction with the Mediator complex, to activate gene expression.[1, 6] | ||
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- | (<jmol><jmolLink> | ||
- | <script> | ||
- | select 261-269; color yellow; trace 0.5; wireframe off; spacefill off; # Highlight 9aaTAD trace | ||
- | selectionHalos ON; delay 1.5; selectionHalos OFF; # Blink selection | ||
- | center selected; zoom 150; | ||
- | </script> | ||
- | <text>Highlight 9aaTAD Transactivation Motif (261-269)</text> | ||
- | </jmolLink></jmol>) | ||
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- | ### Predicted Disordered Regions | ||
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- | Consistent with many transcription factors, large portions of Msn2 are predicted to be intrinsically disordered, lacking a fixed 3D structure.[1, 6] These regions, primarily in the N-terminal half, correspond to areas of low confidence (yellow/red) in the AlphaFold model.[5, 6] Key disordered regions annotated by UniProt include residues 84-246, 418-437, and 592-634.[1] These flexible regions are functionally important, housing regulatory signals like the NLS and NES, phosphorylation sites, and interaction motifs for partners like Mediator.[4, 6] | ||
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- | (<jmol><jmolLink> | ||
- | <script> | ||
- | select all; cartoon on; color cartoon lightgrey; wireframe off; spacefill off; # Reset to grey cartoon | ||
- | select 84-246, 418-437, 592-634; color cartoon orange; # Color annotated disordered regions orange | ||
- | selectionHalos ON; delay 1.5; selectionHalos OFF; # Blink selection | ||
- | center protein; zoom 100; | ||
- | </script> | ||
- | <text>Highlight Predicted Disordered Regions (84-246, 418-437, 592-634)</text> | ||
- | </jmolLink></jmol>) | ||
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- | ### Key PKA Phosphorylation Sites | ||
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- | Msn2 localization and activity are heavily regulated by phosphorylation, particularly by cAMP-dependent Protein Kinase A (PKA).[2, 4] PKA phosphorylation generally inhibits Msn2 function by promoting its cytoplasmic retention.[2, 4] Key PKA target sites include Serines 582, 620, 625, and 633 within the Nuclear Localization Signal (NLS), which inhibit nuclear import [7, 4], and Serine 288 near the Nuclear Export Signal (NES), which promotes nuclear export.[4] Click the link to highlight the sidechains of these five critical serine residues. | ||
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- | (<jmol><jmolLink> | ||
- | <script> | ||
- | select 288, 582, 620, 625, 633; color red; spacefill 100%; wireframe off; # Show PKA site sidechains | ||
- | selectionHalos ON; delay 1.5; selectionHalos OFF; # Blink selection | ||
- | center selected; zoom 150; | ||
- | </script> | ||
- | <text>Highlight Key PKA Phosphorylation Sites (S288, S582, S620, S625, S633)</text> | ||
- | </jmolLink></jmol>) |
Revision as of 14:14, 5 May 2025
- Msn2 (P33748): Interactive Structure of a Yeast Stress-Responsive Transcription Factor
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