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Published online before print June 3, 2005, 10.1110/ps.051387005
Protein Science (2005), 14:1811-1817. Published by Cold Spring Harbor Laboratory Press. Copyright © 2005 The Protein Society
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Urea-induced denaturation of apolipoprotein serum amyloid A reveals marginal stability of hexamer

Limin Wang1 and Wilfredo Colón

Rensselaer Polytechnic Institute, Department of Chemistry and Chemical Biology, Troy, New York 12180, USA

(RECEIVED January 31, 2005; FINAL REVISION April 14, 2005; ACCEPTED April 17, 2005)

Serum Amyloid A (SAA) is an acute phase reactant protein that is predominantly found bound to high-density lipoprotein in plasma. Upon inflammation, the plasma concentration of SAA can increase dramatically, occasionally leading to the development of amyloid A (AA) amyloidosis, which involves the deposition of SAA amyloid fibrils in major organs. We previously found that the murine isoform SAA2.2 exists in aqueous solution as a hexamer containing a central channel. Here we show using various biophysical and biochemical techniques that the SAA2.2 hexamer can be totally dissociated into monomer by ~2 M urea, with the concerted loss of its {alpha}-helical structure. However, limited trypsin proteolysis experiments in urea showed a conserved digestion profile, suggesting the preservation of major backbone topological features in the urea-denatured state of SAA2.2. The marginal stability of hexameric SAA2.2 and the presence of residual structure in the denatured monomeric protein suggest that both forms may interconvert in vivo to exert different functions to meet the various needs during normal physiological conditions and in response to inflammatory stimuli.

Keywords: amyloidosis; HDL; inflammation; acute phase; amyloid fibril

Abbreviations: SAA, serum amyloid A • MOPS, 3-(N-morpholino) propanesulfonic acid • Tris, 2-amino-2-hydroxymethyl-1,3-propanediol • GCL, Glutaraldehyde cross-linking • SEC, size exclusion chromatography • CD, circular dichroism • RT, room temperature • {lambda}max, wavelength of maximum fluorescence emission • MRE or {theta}, molar residue ellipticity

Article published online ahead of print. Article and publication date are at http://www.proteinscience.org/cgi/doi/10.1110/ps.051387005.

Reprint requests to: Wilfredo Colón, Rensselaer Polytechnic Institute, Department of Chemistry and Chemical Biology, 110 8th Street, Troy, NY 12180, USA; e-mail: colonw{at}rpi.edu; fax: (518) 276-4887.


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