Membrane binding of β2-glycoprotein I can be described by a two-state reaction model: An atomic force microscopy and surface plasmon resonance study

Roland Gamsjaeger, Alexander Johs, Anna Gries, Hermann J. Gruber, Christoph Romanin, Ruth Prassl, Peter Hinterdorfer

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

Complexes formed between β2GPI (β2- glycoprotein I), a human plasma protein, and biological membranes are considered to be targets of macrophages and antiphospholipid autoantibodies involved in autoimmune diseases, such as antiphospholipid syndrome or systemic lupus erythematosus. The positively charged lysine-rich fifth domain of β2GPI facilitates its interaction with phospholipid membranes containing acidic phospholipids, which normally become exposed by apoptotic processes. In the present study, atomic force microscopy was applied to visualize the binding of β2GPI to a mixed phospholipid model membrane at physiological ionic strength. On supported lipid bilayers the formation of supramolecular assemblies of the protein with a height of approx. 3.3 nm was observed, suggesting a lateral agglomeration of β 2GPI. Detailed analysis of kinetic constants using surface plasmon resonance revealed that the binding can be described by a two-state reaction model, i.e. a very fast interaction step, depending on the content of acidic phospholipids in the bilayer, and a second step with significantly lower k on and koff values. Taken together, our results suggest a biphasic interaction mechanism: a fast step of β2GPI binding to negatively charged lipids, mainly based on electrostatic interactions, and a slower phase of agglomeration of the protein on the bilayer surface accompanied by a protein-induced rigidification of the membrane, as revealed by electron paramagnetic resonance.

Original languageEnglish
Pages (from-to)665-673
Number of pages9
JournalBiochemical Journal
Volume389
Issue number3
DOIs
StatePublished - Aug 1 2005
Externally publishedYes

Keywords

  • Antiphospholipid syndrome
  • Apolipoprotein H
  • Atomic force microscopy (AFM)
  • Lupus
  • Surface plasmon resonance (SPR)
  • β-glycoprotein I

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