2009 Fiscal Year Final Research Report
Elucidation of molecular mechanisms of lipid metabolism regulation and amyloidogenesis by serum amyloid A.
| Project/Area Number |
20790045
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Physical pharmacy
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| Research Institution | Kobe Pharmaceutical University |
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Principal Investigator |
TANAKA Masafumi Kobe Pharmaceutical University, 薬学部, 講師 (40411904)
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| Project Period (FY) |
2008 – 2009
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| Research Abstract |
Human serum amyloid A (SAA) protein is an apolipoprotein predominantly present in the high-density lipoprotein fraction of plasma. Despite its critical roles in lipid metabolism, especially in acute phases, systematic understanding of the lipid interaction of this protein is limited. SAA shares certain structural features with other apolipoproteins including amphipathic helices, a motif that appears to be responsible for lipid binding. Previously, we examined the lipid-binding properties of the putative amphipathic α-helices in apoA-I molecule using its fragment peptides. In the present study, lipid-binding properties of synthetic fragment peptides corresponding to the N-terminal (region spanning residues 1-27), central (residues 43-63), and C-terminal (residues 77-104) parts of human SAA molecule were examined. SAA (1-27) peptide binds to lipid forming an α-helical structure, whereas SAA (43-63) and (77-104) peptides do not display binding to lipid with any conformational changes. These results indicate that the N-terminal region of SAA is important for lipid interaction. In addition, the finding that proline substitution at 7th residue in the most N-terminal region markedly decreased the binding to lipid indicates that the α-helical structure in this region is essential for lipid binding of SAA. Furthermore, binding competition assay suggests that the replacement of apoA-I in HDL might be caused by membrane disruption by insertion of the N-terminal helix of SAA.
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