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Murine apolipoprotein serum amyloid A in solution forms a hexamer containing a central channel.

Serum amyloid A (SAA) is a small apolipoprotein that binds to high-density lipoproteins in the serum. Although SAA seems to play a role in host defense and lipid transport and metabolism, its specific functions have not been defined. Despite the growing implications that SAA plays a role in the pathology of various diseases, a high-resolution structure of SAA is lacking because of limited solubility in the high-density lipoprotein-free form. In this study, complementary methods including glutaraldehyde cross-linking, size-exclusion chromatography, and sedimentation-velocity analytical ultracentrifugation were used to show that murine SAA2.2 in aqueous solution exists in a monomer-hexamer equilibrium. Electron microscopy of hexameric SAA2.2 revealed that the subunits are arranged in a ring forming a putative central channel. Limited trypsin proteolysis and mass spectrometry analysis identified a significantly protease-resistant SAA2.2 region comprising residues 39-86. The isolated 39-86 SAA2.2 fragment did not hexamerize, suggesting that part of the N terminus is involved in SAA2.2 hexamer formation. Circular-dichroism spectrum deconvolution and secondary-structure prediction suggest that SAA2.2 contains approximately 50% of its residues in alpha-helical conformation and <10% in beta-structure. These findings are consistent with the recent discovery that human SAA1.1 forms a membrane channel and have important implications for understanding the 3D structure, multiple functions, and pathological roles of this highly conserved protein.

Pubmed ID: 12456883


  • Wang L
  • Lashuel HA
  • Walz T
  • Colon W


Proceedings of the National Academy of Sciences of the United States of America

Publication Data

December 10, 2002

Associated Grants

  • Agency: NIGMS NIH HHS, Id: GM62580

Mesh Terms

  • Amyloidosis
  • Animals
  • Biopolymers
  • Chromatography, Gel
  • Chromatography, High Pressure Liquid
  • Circular Dichroism
  • Cross-Linking Reagents
  • Glutaral
  • Mass Spectrometry
  • Mice
  • Microscopy, Electron
  • Protein Structure, Secondary
  • Recombinant Fusion Proteins
  • Serum Amyloid A Protein
  • Structure-Activity Relationship
  • Trypsin
  • Ultracentrifugation