2025-11-29T09:43:06Z

Student:

== Structure ==
<StructureSection load='8ZXD' size='340' side='right' caption='Cryo-EM structure of human Vangl1 (PDB: 8ZXD)' scene=''>
</StructureSection>

This page describes the cryo-EM structure of the human planar cell polarity (PCP) core protein **Vangl1**, determined at high resolution and deposited as **PDB ID: 8ZXD**. The structure reveals the oligomeric assembly and membrane-embedded architecture of Vangl1.

== Function ==

Vangl1 is a core component of the **planar cell polarity pathway**, required for the asymmetric organization of epithelial cells.
It interacts with other PCP proteins such as Prickle, Dishevelled, and Celsr, helping establish directional cues during development.

== Disease relevance ==

Mutations in Vangl1 are associated with **neural tube defects**, disrupted epithelial morphogenesis, and defects in directional cell movement.
Understanding the structure of Vangl1 (8ZXD) provides insights into how disease-causing mutations impair PCP signaling.

== Structural highlights ==

• The 8ZXD cryo-EM structure reveals Vangl1 forms a **stable oligomeric assembly**.
• Multiple **transmembrane helices** form a curved architecture suited for membrane integration.
• The **cytoplasmic C-terminal tail** contains potential interaction motifs for PCP partners.
• Structural comparisons indicate how mutations may disrupt folding, oligomerization, or partner binding.

== References ==
<references/>

<ref>Zhang F, Li S, Wu H, Chen S. Cryo-EM structure and oligomerization of the human planar cell polarity core protein Vangl1. Nature Communications. 2025;16:135.</ref>

== 🧬 Title ==
Structure and Functional Insights of human VANGL1

== 🧬 Summary ==
VANGL1 is a core component of the planar cell polarity (PCP) pathway, which coordinates the orientation of cells across the epithelial plane. This is critical for tissue morphogenesis and developmental processes. Mutations in VANGL1 are linked to congenital defects, including neural tube malformations.

A recent cryo‑electron microscopy (cryo‑EM) study resolved the full-length human VANGL1 structure at 2.9 Å resolution (PDB: 8ZXD), revealing that VANGL1 assembles as a **hexamer**, organized as a **dimer of trimers**. Each trimer consists of four transmembrane helices per protomer followed by cytosolic “hand” and “stick” domains.

The central feature of the hexamer is a **large vestibule**, potentially solvent-filled and sealed from the cytosol when two trimers dimerize. The physiological role of this vestibule is still under investigation. Functional assays suggest that oligomerization enhances VANGL1 binding to the cytosolic effector Prickle1 (Pk1).

Mapping of disease-associated mutations onto the 3D structure indicates that many mutations cluster around the transmembrane region or central vestibule. This implies that disrupted lipid binding, oligomerization, or vestibule integrity may underlie developmental defects.

Overall, the structural data provides a framework for understanding how VANGL1 oligomerization, membrane insertion, and effector interactions contribute to PCP signaling and how mutations cause disease.

== Key Structural Insights ==
- **Hexamer assembly**: VANGL1 forms a dimer of trimers.
- **Domain architecture**: Each protomer has 4 TM helices + cytosolic “hand” and “stick” domains; central vestibule forms upon trimer dimerization.
- **Effector binding**: Hexamerization promotes binding to Prickle1 (Pk1).
- **Disease relevance**: Mutations cluster in TM helices or vestibule → potential disruption of lipid binding or oligomerization.

== Images ==
[[File:VANGL1_stick_interface.png|thumb|Overall hexameric assembly of VANGL1 (dimer of trimers)]]
[[File:VANGL1_heramer.png|thumb|Side-view highlighting transmembrane helices and membrane orientation]]
[[File:VANGL1_trimer_vestibule.png|thumb|Cross-section showing central vestibule and putative lipid-binding site]]

== PyMOL Scripts ==
# Overall hexamer view
fetch 8ZXD, async=0
show cartoon
color cyan, chain A
color yellow, chain B
color salmon, chain C
color gray, chain D
color green, chain E
color orange, chain F
orient
png VANGL1_overview.png, dpi=300

# Membrane/side view
fetch 8ZXD, async=0
show cartoon
show surface, chain A+B+C+D+E+F
set opaque_background, off
orient
png VANGL1_membrane_view.png, dpi=300

# Central vestibule cross-section
fetch 8ZXD, async=0
show cartoon
slice z, 0.0 # adjust plane to intersect vestibule
png VANGL1_central_vestibule.png, dpi=300

Talk:Sandbox karthika project001

2025-11-29T09:11:52Z

Student: New page: == Structure == <StructureSection load='8ZXD' size='340' side='right' caption='Cryo-EM structure of human Vangl1 (PDB: 8ZXD)' scene=''> </StructureSection> This page describes the cryo-EM...

File:Vangl1 hexamer.png

2025-11-29T09:09:48Z

2025-11-28T20:13:26Z

Student:

<table width="90%" border="0"><tr><td>
{| align="left"
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</td></tr><tr><td>

<span style="font-size:180%"><b> Cryo-EM structures of the ''E. coli'' Ton and Tol
motor complexes</b></span>
</td></tr><tr><td>

<span style="font-size:110%">
Paul C. Rosen, Samantha M. Horwitz, Daniel J. Brooks, Erica Kim, Joseph A. Ambarian, Lidia Waidmann, Katherine M. Davis and Gary Yellen
Herve Celia, Bridgette M. Beach, Istvan Botos ,Rodolfo Ghirlando, Denis Duché ,RolandLloubes2 & Susan K. Buchanan
Nature Communications volume 16, Article number: 5506 (2025) [ https://doi.org/10.1038/s41467-025-61286-z]
</span>
</td></tr></table>

==Structure Tour==

<StructureSection load='9DDM' size='350' side='right' caption='Cryo-EM structures of the E. coli Ton and Tol
motor complexes (PDB entry [[9DDM]])' scene=''>
The Ton and Tol systems are proton‑driven motor complexes that are essential for high‑affinity nutrient uptake and for maintaining outer‑membrane integrity in Gram‑negative bacteria. Their activity depends on coordinated interactions among the inner‑membrane proteins ExbB–ExbD–TonB and TolQ–TolR–TolA, but the structural basis of these interactions has been poorly understood. This paper presents near-atomic-resolution cryo-EM structures of both complexes, revealing a conserved architecture in which a pentameric ExbB or TolQ ring encloses a dimeric ExbD or TolR transmembrane segment.
===Overview ===
Gram-negative bacteria use specialized molecular “motors” in their inner membrane to move energy from the proton motive force (pmf) to the cell surface. The ''E. coli'' TolAQR and TonB–ExbBD complexes are two such molecular motors in the inner membrane that harness the proton motive force (pmf) to drive critical cell envelope processes. Despite acting in parallel pathways with the Tol system maintaining outer membrane integrity and the Ton system powering nutrient import, both complexes share similar architectural design: : pentameric scaffold, embedded proton-linked residues, and a single force-transducing helix (TolA or TonB) that connects the pmf machinery to the cell surface. High-resolution cryo-EM structures shown in this paper reveal how these assemblies are organized and how their subunits couple pmf to mechanical action.
===Structure of the ''E. coli'' TolAQR Complex ===
<scene name='10/1096810/9ddm/1'>(9DDM)</scene>
The cryo-EM structure of the TolA–TolQ–TolR complex was obtained after removing the flexible periplasmic portion of TolA which created heterogeneity. This removal was done via a TEV-cleavable construct. The resulting assembly has a 5:2:2 TolQ:TolR:TolA stoichiometry. <scene name='10/1096810/Tolq_pentamer/1'>TolQ Pentamer</scene> forms a pentameric scaffold of seven α-helices per subunit, including three tilted transmembrane helices shaped by conserved proline-induced kinks. TolR forms a dimer within the central hydrophobic pore, with its essential residue<scene name='10/1096810/Asp_in_tolr/1'> Asp23</scene> positioned near a ring of TolQ Thr138/Thr178, creating a proton-linked polar gate. The two<scene name='10/1096810/Tola/1'> TolA</scene> transmembrane helices bind peripherally through the conserved SHLS motif, with His22 making key contacts with TolQ. The cytoplasmic domain of TolQ helices are intrinsically flexible showing dynamic nature during pmf driven activities
===Structure of the ''E. coli''TonB–ExbBD Complex ===
<scene name='10/1096810/9ddp/1'>(9DDP)</scene>
The E. coli TonB–ExbBD complex is a 1:5:2 assembly in which five ExbB subunits form a tilted-helix pentameric scaffold that encloses a parallel but axially offset dimer of ExbD transmembrane helices. The ExbB pentamer generates a hydrophobic central pore into which the ExbD TM dimer inserts, while the N-terminal cytoplasmic domains of ExbD form an asymmetric pair stabilized by conserved ExbB residues. The TonB forms a single transmembrane helix with a conserved SHLS motif. The transmembrane helix is tilted ~15° in the membrane and interacts with the ExbB through conserved TonB Ser16 and His20. The complex also contains tightly bound phosphatidylethanolamine lipids at ExbB subunit interfaces.

===References===

Celia, H., Botos, I., Ghirlando, R., Duché, D., Beach, B. M., Lloubes, R., & Buchanan, S. K. (2025). Cryo-EM structures of the E. coli Ton and Tol motor complexes. Nature Communications, 16, 5506. [https://doi.org/10.1038/s41467-025-61286-z](https://doi.org/10.1038/s41467-025-61286-z)

===About this Page===

This page was created by '''[[User:Your_Username| Niranjana Vinod]]'''.<br>
University/Institution Name (Indian Institute of Science Education and Research,Pune)

</StructureSection>