Interaction of β2-glycoprotein 1 with phosphatidylserine-containing membranes

Ligand-dependent conformational alterations initiate bivalent binding

Randala Hamdan, Sourindra N. Maiti, Alan J. Schroit

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

β2-Glycoprotein 1 (β2GP1), a 50 kDa serum glycoprotein that binds anionic phospholipid-containing membranes, plays a regulatory role in physiology and pathology. The protein is a member of the short consensus repeat (SCR) superfamily containing four typical repeating domains and an aberrant fifth domain constructed into an SCR-like core at the C-terminus. To investigate the contribution of the individual domains to the binding of β2GP1, a series of sequential domain-deleted recombinant protein fragments were generated and assessed for their interaction with PS-containing vesicles. Spectral analyses of lipid binding-dependent alterations in tryptophan emission spectra revealed that the (single) tryptophan residues of the individual domains underwent binding-dependent conformational alterations. Depending on the ionic strength, some domains moved from polar to nonpolar environments, while others moved from less polar to more polar environments. Analysis of a series of acrylamide quenching and resonance energy transfer experiments indicated that the binding of N-terminal domain 1 to PS membranes exists in two, ionic strength-dependent, conformations. At low ionic strengths, domain 1 bound to the vesicles and induced their precipitation and/or aggregation. At physiologic ionic strengths, domain 1 detached from the membrane surface while the remaining domains maintained their association with the membrane. Under these conditions, membrane-bound conformationally altered domain 1 projects away from the membrane surface, enabling it to interact with other proteins and/or cell surface ligands or receptors.

Original languageEnglish (US)
Pages (from-to)10612-10620
Number of pages9
JournalBiochemistry
Volume46
Issue number37
DOIs
StatePublished - Sep 18 2007

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Phosphatidylserines
Glycoproteins
Ligands
Ionic strength
Membranes
Osmolar Concentration
Tryptophan
Acrylamide
Energy Transfer
Physiology
Pathology
Recombinant Proteins
Energy transfer
Conformations
Quenching
Phospholipids
Membrane Proteins
Proteins
Agglomeration
Association reactions

ASJC Scopus subject areas

  • Biochemistry

Cite this

Interaction of β2-glycoprotein 1 with phosphatidylserine-containing membranes : Ligand-dependent conformational alterations initiate bivalent binding. / Hamdan, Randala; Maiti, Sourindra N.; Schroit, Alan J.

In: Biochemistry, Vol. 46, No. 37, 18.09.2007, p. 10612-10620.

Research output: Contribution to journalArticle

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