From Proteopedia

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

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

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References