Aggregation of beta(2)-glycoprotein I induced by sodium lauryl sulfate and lysophospholipids.
beta(2)-Glycoprotein I (beta(2)-GPI) is a plasma protein that binds to negatively charged substances such as DNA, heparin, and anionic phospholipids. The interaction of beta(2)-GPI with anionic phospholipids is intriguing in the context of the autoimmune disease antiphospholipid syndrome. To extend understanding of the binding mechanism to phospholipids, the interactions of beta(2)-GPI with amphiphiles, i.e., sodium lauryl sulfate and lysophospholipids, were examined. These amphiphiles induced the aggregation of beta(2)-GPI below the critical micelle concentration, indicating that the interaction of beta(2)-GPI with monodispersed amphiphiles is unstable, resulting in the formation of large aggregates. However, highly soluble monocaproylphosphatidic acid did not induce aggregation, suggesting that the hydrophobicity of the acyl chain 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 beta(2)-GPI (domain V) is responsible for formation of aggregates observed for intact full-length beta(2)-GPI. In addition, the flexible loop (F307-C326) in the C-terminal of domain V, which consists of hydrophobic and positively charged residues, was identified as the important region for aggregation. These results indicate that beta(2)-GPI binds to the amphiphiles through the flexible loop of domain V, resulting in formation of large aggregates where both electrostatic and hydrophobic interactions are involved.
Hagihara
Yoshihisa
Y
Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Hong
Dong-Pyo
DP
Hoshino
Masaru
M
Enjyoji
Kei-ichi
K
Kato
Hisao
H
Goto
Yuji
Y
D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D006023:Glycoproteins / Q000737:chemistry*; D006801:Humans; D007700:Kinetics; D008246:Lysophospholipids; D008562:Membrane Glycoproteins / Q000737:chemistry; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry; D011485:Protein Binding; D011994:Recombinant Proteins / Q000737:chemistry; D012967:Sodium Dodecyl Sulfate; D053482:beta 2-Glycoprotein I
D006023:Glycoproteins; D008246:Lysophospholipids; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D011994:Recombinant Proteins; D053482:beta 2-Glycoprotein I; D012967:Sodium Dodecyl Sulfate