JMS/Sandbox/msn2 1

<StructureSection size='340' side='right' caption='Caption for this structure' scene=''>

<scene name='10/1080617/Msn2/1'>TextToBeDisplayed</scene>

</StructureSection>

<jmol>

<jmolButton>

<script>

select all; cartoon on; color gray;

select 270-300; cartoon off; spacefill 180; color magenta;

select 573-590 or 620-639; cartoon off; spacefill 180; color lime;

select 642-704; cartoon off; spacefill 180; color orange;

</script>

<text>show entire protein in gray cartoon, NES in magenta, NLS in lime, DBD in orange</text>

</jmolButton>

</jmol>

The 3D structure shown is a predicted model from AlphaFold, providing insights into Msn2’s fold, as no experimental structures are currently available. The model is based on the 704-amino-acid sequence from [UniProt: P33748](https://www.uniprot.org/uniprotkb/P33748/entry).

=== Interactive Molecular Tour ===

Explore Msn2’s structural features using the buttons below, powered by JSmol scripts adapted from the [JSmol documentation](https://chemapps.stolaf.edu/jmol/docs/):

<jmolButton>

<script>select all; cartoon on; color structure; spacefill off;</script>

<script>select 649-670; color red; select 649 and atomName=CA; label "Zinc Finger 1"; select 676-698; color blue; select 676 and atomName=CA; label "Zinc Finger 2";</script>

<script>select 288; spacefill on; color yellow; select 288 and atomName=CA; label "S288"; select 582; spacefill on; color yellow; select 582 and atomName=CA; label "S582"; select 620; spacefill on; color yellow; select 620 and atomName=CA; label "S620"; select 625; spacefill on; color yellow; select 625 and atomName=CA; label "S625"; select 633; spacefill on; color yellow; select 633 and atomName=CA; label "S633"; select 686; spacefill on; color yellow; select 686 and atomName=CA; label "S686";</script>

<script>select all; backbone 0.5; color chain; cartoon off; spacefill off;</script>

<script>reset; labels off; select all; cartoon on; color structure; spacefill off;</script>

<text>Reset View</text>

</jmolButton>

Msn2 has two C2H2 zinc finger domains at residues 649–670 and 676–698, critical for binding STREs (5'-CCCCT-3') in DNA ([SGD: MSN2](https://www.yeastgenome.org/locus/S000004640)). These domains, identified in the sequence (NP_013751.1), coordinate zinc ions via cysteine and histidine residues, stabilizing the DNA-binding motif.

Msn2 is phosphorylated on 22 residues, with six key sites regulated by PKA: S288, S582, S620, S625, S633, and S686. These sites, particularly within the nuclear localization signal (NLS), control Msn2’s shuttling between cytoplasm and nucleus, impacting its transcriptional activity ([Gallmetzer et al., 2018](https://www.molbiolcell.org/doi/10.1091/mbc.E18-06-0389)).

The structure is an AlphaFold-predicted model, offering a reliable depiction of Msn2’s 704-amino-acid structure. AlphaFold’s deep learning approach predicts the protein’s fold, including the zinc finger domains and regions containing phosphorylation sites, based on the sequence from [UniProt: P33748](https://www.uniprot.org/uniprotkb/P33748/entry).

* [UniProt: P33748 (MSN2_YEAST)](https://www.uniprot.org/uniprotkb/P33748/entry)

* [SGD: MSN2 Locus Summary](https://www.yeastgenome.org/locus/S000004640)

* [Constitutive Active Allele of Msn2 Mimicking Low PKA Activity](https://www.molbiolcell.org/doi/10.1091/mbc.E18-06-0389)

* [JSmol Interactive Scripting Documentation](https://chemapps.stolaf.edu/jmol/docs/)

Below is an example of a **Proteopedia page** for Msn2 from budding yeast (*Saccharomyces cerevisiae*) that you can **copy-paste** in its entirety. It uses **inline JSmol scripting** to highlight features such as the DNA-binding Zn-finger domain, disordered regions, phosphorylation sites, and nuclear localization signals (NLS). The Jmol commands are adapted from [Jmol’s documentation](https://chemapps.stolaf.edu/jmol/docs/). Adjust scene names, residue ranges, and color schemes as desired.

|title=Msn2 from Saccharomyces cerevisiae (AlphaFold model)

== Overview of the AlphaFold Structure ==

<StructureSection size='340' side='right' caption='AlphaFold Model of Msn2' scene='Msn2_mainScene'>

<scene name='Msn2_mainScene' script="

# Load and basic display setup

select all

cartoons on

wireframe off

spacefill off

color structure

# Optional background color

background white

# Spin the molecule for an interactive look

spin on

# Center and zoom to show the overall structure

center all

zoom 140

">

This main scene shows the overall predicted structure of Msn2 based on AlphaFold.

</scene>

Msn2 is predominantly disordered throughout its N-terminal half, encompassing the so-called transcriptional activation domain, which interacts with cofactors. However, the C-terminal half contains two C2H2 zinc fingers (residues ~624–704) that bind DNA. Multiple phosphorylation sites modulate its nucleocytoplasmic localization and transcriptional activity, including key sites near the nuclear localization signals (NLS).

== Highlighting the DNA-Binding Zn-Finger Domain ==

<scene name='Msn2_ZnFinger' script="

# Turn on cartoon, color it uniformly for context

select all

cartoons on

color grey

# Highlight the Zn-finger domain (e.g., ~624-704) in orange

select 624-704

color orange

# Center on the middle of the Zn-fingers and zoom in

center 660

zoom 200

# Optionally label the domain

label /1:660 'Zn-Finger Domain'

">

Here we highlight the zinc-finger domain (residues ~624–704), which is essential for DNA binding.

</scene>

These two C2H2 zinc fingers recognize STRE (stress response element) sequences in promoters of stress-related genes.

== Visualizing Intrinsically Disordered Regions ==

<scene name='Msn2_Disorder' script="

# Show entire protein in a thin trace

select all

wireframe 100

spacefill off

cartoons off

color grey

# Now show the structured Zn-finger portion in a cartoon, for contrast

select 624-704

wireframe off

cartoons on

color cyan

# Provide a textual label illustrating the boundary

label /1:650 'N-term (mostly disordered)'

label /1:680 'C-term Zn-Finger'

zoom 140

">

Most of the N-terminal half of Msn2 is predicted to be disordered and flexible, while the C-terminal Zn-finger domain adopts a well-defined fold.

</scene>

Many phosphorylation sites lie within this disordered N-terminus, providing rapid and dynamic control of Msn2’s function.

== Phosphorylation Sites (PKA Target Serines) ==

<scene name='Msn2_Phosphosites' script="

# Start with a cartoon view

select all

cartoons on

color white

spacefill off

# Highlight key serines known to be phosphorylated (e.g., near NLS)

# For demonstration, we list typical PKA sites: S582, S620, S625, S633, S638

select 582,620,625,633,638

spacefill 200

color red

# Label each site

label /1:582 'S582'

label /1:620 'S620'

label /1:625 'S625'

label /1:633 'S633'

label /1:638 'S638'

# Center on the region around residue 620

center 620

zoom 200

">

Several serines in the vicinity of the nuclear localization signals are phosphorylated by PKA. Under non-stress conditions, these phosphorylations contribute to cytoplasmic retention of Msn2.

</scene>

Dephosphorylation of these sites during stress permits nuclear entry and gene activation.

== Nuclear Localization Signals (NLS) ==

<scene name='Msn2_NLS' script="

# C-terminal region in cartoon

select all

cartoons on

color grey

# Color the NLS clusters in green (e.g., around 573–590 and 620–639)

select 573-590 or 620-639

color green

# Center and zoom to show the NLS near the Zn-finger domain

center 600

zoom 180

# Optional: turn on spin for a dynamic look

spin on

">

Two NLS segments in Msn2 are highlighted in green. Their phosphorylation state determines nuclear import efficiency.

</scene>

== Measuring Zn-Finger Coordination (Example of a Distance Measure) ==

<scene name='Msn2_DistanceMeasure' script="

# Turn off any previous measures

measure delete *

# Show cartoon for context

select all

cartoons on

color grey

# Identify (example) two Zn-coordinating residues in the first Zn finger

# Let's say these are Cys626 and His630 (fictitious example positions)

select 626, 630

spacefill 200

color yellow

label /1:626 'Cys626'

label /1:630 'His630'

# Measure the distance

measure distance {1:626} {1:630}

color measures black

# Center on Zn-finger and zoom

center 628

zoom 250

">

This scene measures the distance between two putative zinc-coordinating residues (Cys626 and His630). Jmol’s ''measure distance'' command is useful to confirm geometry around metal-binding sites.

</scene>

== Nuclear Export Signal (NES) Region ==

<scene name='Msn2_NES' script="

# Show cartoon for the entire protein

select all

cartoons on

color grey

# Emphasize the NES region (e.g., ~270–300)

select 270-300

cartoons off

wireframe 150

color magenta

# Provide labels

label /1:288 'Ser288'

center 288

zoom 200

">

A leucine-rich NES around residues 270–300, including Ser288, regulates nuclear export of Msn2. Phosphorylation here also modulates cytoplasmic retention.

</scene>

== Additional Notes ==

* The above scenes illustrate different regulatory features of Msn2.

* Residue numbering may vary in different Msn2 isoforms or structural models.

* For real structural validation, consider comparing with experimental data if available.

== References ==

* Görner, W., et al. (2002). ''Nuclear localization of the C2H2 zinc finger protein Msn2 is regulated by stress and protein kinase A activity in yeast.'' EMBO J. **21**(1):135–144.

* Gasch, A.P., et al. (2000). ''Genomic expression programs in the response of yeast cells to environmental changes.'' Mol. Biol. Cell. **11**(12):4241–4257.

* De Wever, V., et al. (2005). ''Phosphorylation of serine 288 in the nuclear export signal of Msn2 by protein kinase A modulates Msn2 nuclear localization.'' J. Biol. Chem. **280**(46):37193–37198.

* AlphaFold Protein Structure Database: [Msn2 (P13382)](https://alphafold.ebi.ac.uk/entry/P13382)

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''Copy and paste the entire text above into a Proteopedia page and adjust the scene names, residue ranges, or color schemes to suit your needs. Each <scene> tag includes an inline JSmol script adapted from [Jmol’s documentation](https://chemapps.stolaf.edu/jmol/docs/). Feel free to tweak them further for your final Msn2 article!''

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**Note**: In Proteopedia, you can embed additional descriptive text or images around these `<scene>` tags. If needed, replace the numeric ranges or residue numbers based on your alignment of Msn2. You may also change the coloring or labeling schemes. This template simply provides a comprehensive starting point for your Msn2 molecular tour!

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