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http://140.128.103.80:8080/handle/310901/24729
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| Title: | Structural basis of specific interactions of Lp-PLA2 with HDL revealed by hydrogen deuterium exchange mass spectrometry |
| Authors: | Cao, J.;Hsu, Y.-H.;Li, S.;Woods, Jr. V.L.;Dennis, E.A. |
| Contributors: | Department of Chemistry, Tunghai University |
| Keywords: | Apolipoproteins;Enzymology;High density lipoprotein;Lipoprotein-associated phospholipase a2 |
| Date: | 2013 |
| Issue Date: | 2014-05-30T02:07:50Z (UTC)
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| Abstract: | Lipoprotein-associated phospholipase A2 (Lp-PLA2), specifically Group VIIA PLA2, is a member of the phospholipase A 2 superfamily and is found mainly associated with LDL and HDL in human plasma. Lp-PLA2 is considered as a risk factor, a potential biomarker, a target for therapy in the treatment of cardiovascular disease, and evidence suggests that the level of Lp-PLA2 in plasma is associated with the risk of future cardiovascular and stroke events. The differential location of the enzyme in LDL/HDL lipoproteins has been suggested to affect Lp-PLA2 function and/or its physiological role and an abnormal distribution of the enzyme may correlate with diseases. Although a mutagenesis study suggested that a surface helix (residues 362-369) mediates the association between Lp-PLA2 and HDL, the molecular details and mechanism of association has remained unknown. We have now employed hydrogen deuterium exchange mass spectrometry to characterize the interaction between recombinant human Lp- PLA2 and human HDL. We have found that specific residues 113-120, 192-204, and 360-368 likely mediate HDL binding. In a previous study, we showed that residues 113-120 are important for Lp-PLA2-liposome interactions. We now find that residues 192-204 show a decreased deuteration level when Lp-PLA2 is exposed to apoA-I, but not apoA-II, the most abundant apoproteins in HDL, and additionally, residues 360-368 are only affected by HDL. The results suggest that apoA-I and phospholipid membranes play crucial roles in Lp-PLA2 localization to HDL. Copyright ? 2013 by the American Society for Biochemistry and Molecular Biology, Inc. |
| Relation: | Apolipoproteins; Enzymology; High density lipoprotein; Lipoprotein-associated phospholipase a2,Vol.54,Issue1,P.127-133 |
| Appears in Collections: | [化學系所] 期刊論文
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