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Artificial intelligence prediction of carcinoembryonic antigen structure and interactions relevant for colorectal cancer

  • 0Endocrine and Sarcoma Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Biochemistry and Biophysics Reports +

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May 7, 2025

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May 7, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Carcinoembryonic antigen (CEA) structure was predicted using AlphaFold 3, revealing bends that explain its dimerization. This provides new insights into CEA

Area Of Science

  • Structural biology
  • Computational biology
  • Biochemistry

Background

  • Carcinoembryonic antigen (CEA) is a biomarker for colorectal cancer with low expression in healthy adults.
  • The tertiary structure of mature, glycosylated CEA has been unavailable due to its complexity.
  • Novel structure prediction methods are needed to understand CEA's structure and interactions.

Purpose Of The Study

  • To investigate the tertiary structure and interactions of carcinoembryonic antigen (CEA).
  • To utilize AlphaFold 3 for accurate protein structure and glycan modeling.
  • To predict the structure of monomeric CEA, dimeric CEA, and CEA in complex with the antibody Tusamitamab.

Main Methods

  • Employed AlphaFold 3 server for novel structure prediction.
  • Modeled monomeric glycosylated CEA, dimeric CEA, and CEA-Tusamitamab complex.
  • Validated complex structure against experimental electron microscopy data.

Main Results

  • Predicted monomeric glycosylated CEA exhibits bends at domain interfaces B1-A2 and B2-A3.
  • Dimeric CEA structure shows parallel pairing with direct contacts between N and A2 domains.
  • CEA-Tusamitamab complex prediction closely matched experimental EM structure (1.3 Å all-atom RMSD).

Conclusions

  • Predicted bends in CEA structure facilitate dimer formation, potentially explaining its biological roles.
  • AlphaFold 3 accurately predicts antibody-protein complexes, even those not in the training set.
  • These findings offer new avenues for investigating CEA structure and function in cancer.

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