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Contents 1 Cryo-EM Structure of Human Serum Albumin (2024) 1.1 Reference Study 1.2 Structure 1.3 Function 1.4 Disease 1.5 Relevance 1.6 Structural Highlights 1.7 Uploaded Figures 1.8 References

Cryo-EM Structure of Human Serum Albumin (2024)

By JHANVI

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

spinqualitylabelsall models Cryo-EM structure of human serum albumin bound to ligands (8VAC, 2024) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image 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: Three-domain organization (I, II, III), each with A/B subdomains. A flexible, heart-shaped tertiary fold. Multiple hydrophobic binding pockets for drugs, fatty acids, and endogenous molecules. Conformational adjustments in Sudlow sites I and II upon ligand engagement. Domain movements consistent with adaptive ligand accommodation. The loaded 8VAC structure provides a solution-like, high-fidelity representation of the molecule.

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