Sandbox my first page 001

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (17:07, 30 November 2025) (edit) (undo)
(Created full sandbox page for 8VAC: added structure overview, functional analysis, ligand-binding highlights, reference citation, image gallery, and uploaded figure.)
 
(2 intermediate revisions not shown.)
Line 1: Line 1:
-
<table width="90%" border="0"><tr><td>
+
= Cryo-EM Structure of Human Serum Albumin (2024) =
-
{| align="left"
+
''By JHANVI KATH BI3323-Aug 2025''
-
|-
+
-
|
+
-
|}
+
-
</td></tr><tr><td>
+
-
<span style="font-size:180%"><b> Cryo-EM structures of the ''E. coli'' Ton and Tol (BI3323-Aug2025)
+
== Reference Study ==
-
motor complexes</b></span>
+
Catalano C., Lucier K. W., To D., Senko S., Tran N. L., Farwell A. C., Silva S. M., Dip P. V., Poweleit N., Scapin G. (2024).
-
</td></tr><tr><td>
+
''The CryoEM structure of human serum albumin in complex with ligands.''
 +
Journal of Structural Biology, 216(3):108105.
 +
DOI: 10.1016/j.jsb.2024.108105
-
<span style="font-size:110%">
+
PDB ID: 8VAC
-
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==
+
== Structure ==
 +
<StructureSection load='8VAC' size='340' side='right' caption='Cryo-EM structure of human serum albumin bound to ligands (8VAC, 2024)' scene=''>
 +
Human Serum Albumin (HSA) is the dominant plasma protein responsible for transport, buffering, and molecular trafficking.
 +
The 2024 cryo-EM map (8VAC) captures HSA in complex with multiple ligands under near-physiological biochemical conditions, revealing:
-
<StructureSection load='9DDM' size='350' side='right' caption='Cryo-EM structures of the E. coli Ton and Tol
+
* Three-domain organization (I, II, III), each with A/B subdomains.
-
motor complexes (PDB entry [[9DDM]])' scene=''>
+
* A flexible, heart-shaped tertiary fold.
-
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.
+
* Multiple hydrophobic binding pockets for drugs, fatty acids, and endogenous molecules.
-
===Overview ===
+
* Conformational adjustments in Sudlow sites I and II upon ligand engagement.
-
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.
+
* Domain movements consistent with adaptive ligand accommodation.
-
===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 </scene> forms a pentameric scaffold of seven α-helices per subunit, including three tilted transmembrane helices shaped by conserved proline-induced kinks. <scene name='10/1096810/Tolr/2'>TolR</scene> 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 <scene name='10/1096810/Tolq/1'>TolQ Thr138/Thr178</scene>, creating a proton-linked polar gate. The two<scene name='10/1096810/Tola/1'> TolA</scene> transmembrane helices bind peripherally through the conserved <scene name='10/1096810/Shls_motif_in_tol_a/1'>SHLS motif</scene>, 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 <scene name='10/1096810/Exbb_pentamer/1'>ExbB</scene> subunits form a tilted-helix pentameric scaffold that encloses a parallel but axially offset dimer of<scene name='10/1096810/Exbd_dimer/1'> ExbD</scene> 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 <scene name='10/1096810/Tonb/1'>TonB</scene> 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 <scene name='10/1096810/Tonb_ser16/2'>Ser16</scene> and <scene name='10/1096810/Tonb_his20/1'>His20</scene>. The complex also contains tightly bound phosphatidylethanolamine lipids at ExbB subunit interfaces.
+
-
===References===
+
The loaded 8VAC structure provides a solution-like, high-fidelity representation of the molecule.
 +
</StructureSection>
-
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)
+
== Function ==
 +
HSA acts as a systemic transport hub in the bloodstream.
 +
Major physiological roles include:
-
===About this Page===
+
* Binding and transport of fatty acids, bilirubin, hormones, and xenobiotics.
-
<!-- This section ensures you get credit -->
+
* Strong influence on pharmacokinetics for albumin-bound drugs.
-
This page was created by '''[[User:Your_Username| Niranjana Vinod BI3323-Aug2025]]'''.<br>
+
* Maintenance of colloid osmotic pressure.
-
University/Institution Name (Indian Institute of Science Education and Research,Pune)
+
* Participation in pH buffering and redox balance.
 +
The 8VAC cryo-EM structure highlights how the protein repositions domains to optimize ligand engagement.
-
</StructureSection>
+
== Disease ==
 +
Structural or concentration changes in HSA correlate with many pathologies:
 +
 
 +
* Hypoalbuminemia in liver disease, sepsis, nephrotic syndrome.
 +
* Glycation and oxidation in diabetes or chronic kidney disease, altering ligand affinity.
 +
* Hereditary albumin variants, impacting stability and drug-binding profiles.
 +
* Altered levels in inflammation, cancer, and severe infection influence drug dosing outcomes.
 +
 
 +
Structural mapping enables correlation of clinical conditions with ligand-pocket geometry.
 +
 
 +
== Relevance ==
 +
The 8VAC structure is directly applicable to:
 +
 
 +
* Drug design – understanding pocket architecture assists affinity and specificity tuning.
 +
* PK/PD modeling – high-affinity albumin binders require dosage fine-tuning.
 +
* Albumin-based drug delivery systems – nanoparticles and small molecules utilize albumin’s long circulation time.
 +
* Biomarker interpretation – albumin concentration is essential in diagnoses and scoring systems.
 +
 
 +
This structure bridges clinical context and molecular understanding in a single cryo-EM model.
 +
 
 +
== Structural Highlights ==
 +
Below are placeholder SAT scenes that you can replace with your own:
 +
 
 +
* Overall 3-domain organization:
 +
<scene name="/sandbox/jhanvi/HSA_8VAC/overall/1">Domain overview</scene>
 +
 
 +
* Sudlow Site I (Domain IIA):
 +
<scene name="/sandbox/jhanvi/HSA_8VAC/siteI/1">Primary drug-binding pocket</scene>
 +
 
 +
* Sudlow Site II (Domain IIIA):
 +
<scene name="/sandbox/jhanvi/HSA_8VAC/siteII/1">Secondary drug-binding pocket</scene>
 +
 
 +
* Flexibility + domain movements:
 +
<scene name="/sandbox/jhanvi/HSA_8VAC/flexibility/1">Hinge flexibility</scene>
 +
 
 +
== Uploaded Figures ==
 +
Insert your PNGs here after uploading (instructions below):
 +
 
 +
<gallery>
 +
File:HSA_Overall_Structure.png|Overall Cryo-EM structure of Human Serum Albumin (8VAC)
 +
File:HSA_Salicylic.png|HSA with salicylic ligand bound
 +
</gallery>
 +
 
 +
== References ==
 +
<references/>

Current revision

Contents

Cryo-EM Structure of Human Serum Albumin (2024)

By JHANVI KATH BI3323-Aug 2025

Reference Study

Catalano C., Lucier K. W., To D., Senko S., Tran N. L., Farwell A. C., Silva S. M., Dip P. V., Poweleit N., Scapin G. (2024). The CryoEM structure of human serum albumin in complex with ligands. Journal of Structural Biology, 216(3):108105. DOI: 10.1016/j.jsb.2024.108105

PDB ID: 8VAC

Structure

Cryo-EM structure of human serum albumin bound to ligands (8VAC, 2024)

Drag the structure with the mouse to rotate

Function

HSA acts as a systemic transport hub in the bloodstream. Major physiological roles include:

  • Binding and transport of fatty acids, bilirubin, hormones, and xenobiotics.
  • Strong influence on pharmacokinetics for albumin-bound drugs.
  • Maintenance of colloid osmotic pressure.
  • Participation in pH buffering and redox balance.

The 8VAC cryo-EM structure highlights how the protein repositions domains to optimize ligand engagement.

Disease

Structural or concentration changes in HSA correlate with many pathologies:

  • Hypoalbuminemia in liver disease, sepsis, nephrotic syndrome.
  • Glycation and oxidation in diabetes or chronic kidney disease, altering ligand affinity.
  • Hereditary albumin variants, impacting stability and drug-binding profiles.
  • Altered levels in inflammation, cancer, and severe infection influence drug dosing outcomes.

Structural mapping enables correlation of clinical conditions with ligand-pocket geometry.

Relevance

The 8VAC structure is directly applicable to:

  • Drug design – understanding pocket architecture assists affinity and specificity tuning.
  • PK/PD modeling – high-affinity albumin binders require dosage fine-tuning.
  • Albumin-based drug delivery systems – nanoparticles and small molecules utilize albumin’s long circulation time.
  • Biomarker interpretation – albumin concentration is essential in diagnoses and scoring systems.

This structure bridges clinical context and molecular understanding in a single cryo-EM model.

Structural Highlights

Below are placeholder SAT scenes that you can replace with your own:

  • Overall 3-domain organization:
  • Sudlow Site I (Domain IIA):
  • Sudlow Site II (Domain IIIA):
  • Flexibility + domain movements:

Uploaded Figures

Insert your PNGs here after uploading (instructions below):

File:HSA Overall Structure.png

Overall Cryo-EM structure of Human Serum Albumin (8VAC)

File:HSA Salicylic.png

HSA with salicylic ligand bound

References

Retrieved from "http://52.214.119.220/wiki/index.php/Sandbox_my_first_page_001"
Personal tools