Serum amyloid A self-assembles with phospholipids to form stable protein-rich
nanoparticles with a distinct structure: A hypothetical function of SAA as a
"molecular mop" in immune response
#MMPMID28645735
Frame NM
; Jayaraman S
; Gantz DL
; Gursky O
J Struct Biol
2017[Dec]; 200
(3
): 293-302
PMID28645735
show ga
Serum amyloid A (SAA) is an acute-phase protein whose action in innate immunity
and lipid homeostasis is unclear. Most circulating SAA binds plasma high-density
lipoproteins (HDL) and reroutes lipid transport. In vivo SAA binds existing
lipoproteins or generates them de novo upon lipid uptake from cells. We explored
the products of SAA-lipid interactions and lipoprotein remodeling in vitro. SAA
complexes with palmitoyl-oleoyl phosphocholine (POPC) were analyzed for structure
and stability using circular dichroism and fluorescence spectroscopy, electron
microscopy, gel electrophoresis and gel filtration. The results revealed the
formation of 8-11nm lipoproteins that were?50% ?-helical and stable at
near-physiological conditions but were irreversibly remodeled at T(m)?52°C.
Similar HDL-size nanoparticles formed spontaneously at ambient conditions or upon
thermal remodeling of parent lipoproteins containing various amounts of proteins
and lipids, including POPC and cholesterol. Therefore, such HDL-size particles
formed stable kinetically accessible structures in a wide range of conditions.
Based on their size and stoichiometry, each particle contained about 12 SAA and
72 POPC molecules, with a protein:lipid weight ratio circa 2.5:1, suggesting a
structure distinct from HDL. High stability of these nanoparticles and their
HDL-like size suggest that similar lipoproteins may form in vivo during
inflammation or injury when SAA concentration is high and membranes from dead
cells require rapid removal. We speculate that solubilization of membranes by SAA
to generate lipoproteins in a spontaneous energy-independent process constitutes
the primordial function of this ancient protein, providing the first line of
defense in clearing cell debris from the injured sites.
|Animals
[MESH]
|Cholesterol/chemistry
[MESH]
|Chromatography, Gel
[MESH]
|Circular Dichroism
[MESH]
|Electrophoresis, Polyacrylamide Gel
[MESH]
|Lipoproteins, HDL/chemistry
[MESH]
|Mice
[MESH]
|Microscopy, Electron
[MESH]
|Nanoparticles/*chemistry
[MESH]
|Particle Size
[MESH]
|Phosphatidylcholines/*chemistry
[MESH]
|Phospholipids/chemistry
[MESH]
|Protein Stability
[MESH]
|Serum Amyloid A Protein/*chemistry/immunology
[MESH]
free
free
free
