title: The interaction of beta(2)-glycoprotein I domain V with chaperonin GroEL: the similarity with the domain V and membrane interaction.
abstract: To clarify the mechanism of interaction between chaperonin GroEL and substrate proteins, we studied the conformational changes; of the fifth domain of human beta(2)-glycoprotein I upon binding to GroEL. The fifth domain has a large flexible loop, containing several hydrophobic residues surrounded by positively charged residues, which has been proposed to be responsible for the binding of beta(2)-glycoprotein I to negatively charged phospholipid membranes. The reduction by dithiothreitol of the three intramolecular disulfide bonds of the fifth domain was accelerated in the presence of stoichiometric amounts of GroEL, indicating that the fifth domain was destabilized upon interaction with GroEL. To clarify the GroEL-induced destabilization at the atomic level, we performed H/(2)H exchange of amide protons using heteronuclear NMR spectroscopy. The presence of GroEL promoted the H/(2)H exchange of most of the protected amide protons, suggesting that, although the flexible loop of the fifth domain is likely to be responsible for the initiation of binding to GroEL, the interaction with GroEL destabilizes the overall conformation of the fifth domain.
authors.affiliation: Institute for Protein Research, Osaka University, Yamadaoka 3-2, Suita, Japan.
authors.forename: Masayo
authors.initials: M
authors.lastname: Gozu
authors.forename: Masaru
authors.initials: M
authors.lastname: Hoshino
authors.forename: Takashi
authors.initials: T
authors.lastname: Higurashi
authors.forename: Hisao
authors.initials: H
authors.lastname: Kato
authors.forename: Yuji
authors.initials: Y
authors.lastname: Goto
mesh_terms: D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000378:metabolism*; D018834:Chaperonin 60 / Q000737:chemistry / Q000378:metabolism*; D004220:Disulfides / Q000378:metabolism; D005453:Fluorescence; D006023:Glycoproteins / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D006859:Hydrogen / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011522:Protons; D014364:Tryptophan / Q000378:metabolism; D053482:beta 2-Glycoprotein I
chemical_list: D018834:Chaperonin 60; D004220:Disulfides; D006023:Glycoproteins; D008565:Membrane Proteins; D011522:Protons; D053482:beta 2-Glycoprotein I; D006859:Hydrogen; D014364:Tryptophan