Aggregation of 2-Glycoprotein I Induced by Sodium Lauryl Sulfate and Lysophospholipids

详细信息    查看全文

• 作者：Yoshihisa Hagihara ; Dong-Pyo Hong ; Masaru Hoshino ; Kei-ichi Enjyoji ; Hisao Kato ; and Yuji Goto
• 刊名：Biochemistry
• 出版年：2002
• 出版时间：January 22, 2002
• 年：2002
• 卷：41
• 期：3
• 页码：1020 - 1026
• 全文大小：92K
• 年卷期：v.41,no.3(January 22, 2002)
• ISSN：1520-4995

文摘

₂-Glycoprotein I (₂-GPI) is a plasma protein that binds to negatively charged substancessuch as DNA, heparin, and anionic phospholipids. The interaction of ₂-GPI with anionic phospholipidsis intriguing in the context of the autoimmune disease antiphospholipid syndrome. To extend understandingof the binding mechanism to phospholipids, the interactions of ₂-GPI with amphiphiles, i.e., sodiumlauryl sulfate and lysophospholipids, were examined. These amphiphiles induced the aggregation of ₂-GPI below the critical micelle concentration, indicating that the interaction of ₂-GPI with monodispersedamphiphiles is unstable, resulting in the formation of large aggregates. However, highly solublemonocaproylphosphatidic acid did not induce aggregation, suggesting that the hydrophobicity of the acylchain is also an important factor for aggregate formation in addition to negative charges in the headgroup.A series of experiments using deletion mutants and a peptide showed that the fifth domain of ₂-GPI(domain V) is responsible for formation of aggregates observed for intact full-length ₂-GPI. In addition,the flexible loop (F307-C326) in the C-terminal of domain V, which consists of hydrophobic and positivelycharged residues, was identified as the important region for aggregation. These results indicate that ₂-GPI binds to the amphiphiles through the flexible loop of domain V, resulting in formation of largeaggregates where both electrostatic and hydrophobic interactions are involved.