The J-elongated conformation of β2-glycoprotein I predominates in solution: Implications for our understanding of antiphospholipid syndrome

Ruben, Eliza; Planer, William; Chinnaraj, Mathivanan; Chen, Zhiwei; Zuo, Xiaobing; Pengo, Vittorio; De Filippis, Vincenzo; Alluri, Ravi K.; McCrae, Keith R.; Macor, Paolo; Tedesco, Francesco; Pozzi, Nicola

doi:10.1074/jbc.RA120.013939

Title: The J-elongated conformation of β₂-glycoprotein I predominates in solution: Implications for our understanding of antiphospholipid syndrome

Journal Article · Fri Jul 31 00:00:00 EDT 2020 · Journal of Biological Chemistry

DOI:https://doi.org/10.1074/jbc.RA120.013939· OSTI ID:1772485

Ruben, Eliza ^[1]; Planer, William ^[1];

^[1]; Chen, Zhiwei ^[1]; Zuo, Xiaobing ^[2]; Pengo, Vittorio ^[3]; De Filippis, Vincenzo ^[4]; Alluri, Ravi K. ^[5]; McCrae, Keith R. ^[5]; Macor, Paolo ^[6];

^[7];

^[1]

Saint Louis Univ., MO (United States)
Argonne National Lab. (ANL), Argonne, IL (United States)
Univ. of Padova (Italy); Arianna Foundation on Anticoagulation, Bologna (Italy)
Univ. of Padua (Italy)
Cleveland Clinic, OH (United States)
Univ. of Trieste (Italy)
Istituto Auxologico Italiano, Milan (Italy)

β₂-Glycoprotein I (β₂GPI) is an abundant plasma protein displaying phospholipid-binding properties. Because it binds phospholipids, it is a target of antiphospholipid antibodies (aPLs) in antiphospholipid syndrome (APS), a life-threatening autoimmune thrombotic disease. Indeed, aPLs prefer membrane-bound β₂GPI to that in solution. β₂GPI exists in two almost equally populated redox states: oxidized, in which all the disulfide bonds are formed, and reduced, in which one or more disulfide bonds are broken. Furthermore, β₂GPI can adopt multiple conformations (i.e. J-elongated, S-twisted, and O-circular). While strong evidence indicates that the J-form is the structure bound to aPLs, which conformation exists and predominates in solution remains controversial, and so is the conformational pathway leading to the bound state. Here, we report that human recombinant β₂GPI purified under native conditions is oxidized. Moreover, under physiological pH and salt concentrations, this oxidized form adopts a J-elongated, flexible conformation, not circular or twisted, in which the N-terminal domain I (DI) and the C-terminal domain V (DV) are exposed to the solvent. Consistent with this model, binding kinetics and mutagenesis experiments revealed that in solution the J-form interacts with negatively charged liposomes and with MBB2, a monoclonal anti-DI antibody that recapitulates most of the features of pathogenic aPLs. We conclude that the preferential binding of aPLs to phospholipid-bound β₂GPI arises from the ability of its preexisting J-form to accumulate on the membranes, thereby offering an ideal environment for aPL binding. We propose that targeting the J-form of β₂GPI provides a strategy to block pathogenic aPLs in APS.

View Accepted Manuscript (DOE)

Cite

Export

Save

Research Organization:: Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: National Institutes of Health (NIH); CaRiPaRo Foundation; USDOE Office of Science (SC), Basic Energy Sciences (BES)

Grant/Contract Number:: AC02-06CH11357; 2018 BPiTA-52012; HL150146; HL049413; HL139554; HL147821

OSTI ID:: 1772485

Alternate ID(s):: OSTI ID: 1774512

Journal Information:: Journal of Biological Chemistry, Vol. 295, Issue 31

Publisher:: American Society for Biochemistry and Molecular BiologyCopyright Statement

Country of Publication:: United States

Language:: English

References (71)

Simulation and Theory of Antibody Binding to Crowded Antigen-Covered Surfaces De Michele, Cristiano; De Los Rios, Paolo; Foffi, Giuseppe PLOS Computational Biology, Vol. 12, Issue 3 https://doi.org/10.1371/journal.pcbi.1004752	journal	March 2016
PAM: A Framework for Integrated Analysis of Imaging, Single-Molecule, and Ensemble Fluorescence Data Schrimpf, Waldemar; Barth, Anders; Hendrix, Jelle Biophysical Journal, Vol. 114, Issue 7 https://doi.org/10.1016/j.bpj.2018.02.035	journal	April 2018
Complete amino acid sequence of human plasma beta 2-glycoprotein I. Lozier, J.; Takahashi, N.; Putnam, F. W. Proceedings of the National Academy of Sciences, Vol. 81, Issue 12 https://doi.org/10.1073/pnas.81.12.3640	journal	June 1984
Impact of Antigen Density on the Binding Mechanism of IgG Antibodies Hadzhieva, Maya; Pashov, Anastas D.; Kaveri, Srinivas Scientific Reports, Vol. 7, Issue 1 https://doi.org/10.1038/s41598-017-03942-z	journal	June 2017
The Pathogenesis of the Antiphospholipid Syndrome Giannakopoulos, Bill; Krilis, Steven A. New England Journal of Medicine, Vol. 368, Issue 11 https://doi.org/10.1056/NEJMra1112830	journal	March 2013
β2-glycoprotein I for binding of anticardiolipin antibodies to cardiolipin Bevers, E.; Galli, M. The Lancet, Vol. 336, Issue 8720 https://doi.org/10.1016/0140-6736(90)92330-K	journal	October 1990
IgG antibodies that recognize epitope Gly40-Arg43 in domain I of β2–glycoprotein I cause LAC, and their presence correlates strongly with thrombosis de Laat, Bas; Derksen, Ronald H. W. M.; Urbanus, Rolf T. Blood, Vol. 105, Issue 4 https://doi.org/10.1182/blood-2004-09-3387	journal	February 2005
Toll-like receptor and antiphospholipid mediated thrombosis: in vivo studies Pierangeli, S. S.; Vega-Ostertag, M. E.; Raschi, E. Annals of the Rheumatic Diseases, Vol. 66, Issue 10 https://doi.org/10.1136/ard.2006.065037	journal	October 2007
β2-glycoprotein-1 autoantibodies from patients with antiphospholipid syndrome are sufficient to potentiate arterial thrombus formation in a mouse model Arad, Ariela; Proulle, Valerie; Furie, Richard A. Blood, Vol. 117, Issue 12 https://doi.org/10.1182/blood-2010-08-300715	journal	March 2011
Dimerized Domain V of Beta2-Glycoprotein I Is Sufficient to Upregulate Procoagulant Activity in PMA-Treated U937 Monocytes and Require Intact Residues in Two Phospholipid-Binding Loops Kolyada, Alexey; Barrios, David; Beglova, Natalia Antibodies, Vol. 6, Issue 2 https://doi.org/10.3390/antib6020008	journal	June 2017
Accurate FRET Measurements within Single Diffusing Biomolecules Using Alternating-Laser Excitation Lee, Nam Ki; Kapanidis, Achillefs N.; Wang, You Biophysical Journal, Vol. 88, Issue 4 https://doi.org/10.1529/biophysj.104.054114	journal	April 2005
Chemical synthesis and characterization of wild-type and biotinylated N-terminal domain 1-64 of β2-glycoprotein I Pozzi, Nicola; Banzato, Alessandra; Bettin, Samuele Protein Science, Vol. 19, Issue 5 https://doi.org/10.1002/pro.387	journal	March 2010
A non–complement-fixing antibody to β2 glycoprotein I as a novel therapy for antiphospholipid syndrome Agostinis, Chiara; Durigutto, Paolo; Sblattero, Daniele Blood, Vol. 123, Issue 22 https://doi.org/10.1182/blood-2013-11-537704	journal	May 2014
Crystal structure of human β2-glycoprotein I: implications for phospholipid binding and the antiphospholipid syndrome Schwarzenbacher, Robert; Zeth, Kornelius; Diederichs, Kay The EMBO Journal, Vol. 18, Issue 22 https://doi.org/10.1093/emboj/18.22.6228	journal	November 1999
The effect of phospholipids on the formation of immune complexes between autoantibodies and β2-glycoprotein I or prothrombin Bevers, Edouard M.; Zwaal, Robert F. A.; Willems, George M. Clinical Immunology, Vol. 112, Issue 2 https://doi.org/10.1016/j.clim.2004.02.009	journal	August 2004
Discovery and characterization of 2 novel subpopulations of aPS/PT antibodies in patients at high risk of thrombosis Chinnaraj, Mathivanan; Planer, William; Pengo, Vittorio Blood Advances, Vol. 3, Issue 11 https://doi.org/10.1182/bloodadvances.2019030932	journal	June 2019
Adhesion mechanism of human beta 2-glycoprotein I to phospholipids based on its crystal structure Bouma, B. The EMBO Journal, Vol. 18, Issue 19 https://doi.org/10.1093/emboj/18.19.5166	journal	October 1999
Toward dynamic structural biology: Two decades of single-molecule Förster resonance energy transfer Lerner, Eitan; Cordes, Thorben; Ingargiola, Antonino Science, Vol. 359, Issue 6373 https://doi.org/10.1126/science.aan1133	journal	January 2018
Allosteric activation of ADAMTS13 by von Willebrand factor Muia, Joshua; Zhu, Jian; Gupta, Garima Proceedings of the National Academy of Sciences, Vol. 111, Issue 52 https://doi.org/10.1073/pnas.1413282112	journal	December 2014
Interdomain Contact Regions and Angles Between Adjacent Short Consensus Repeat Domains Lehtinen, Markus J.; Meri, Seppo; Jokiranta, T. Sakari Journal of Molecular Biology, Vol. 344, Issue 5 https://doi.org/10.1016/j.jmb.2004.10.017	journal	December 2004
Anticardiolipin antibodies and β2-glycoprotein I Koike, T.; Matsuura, E. Lupus, Vol. 5, Issue 2 https://doi.org/10.1177/096120339600500213	journal	April 1996
Beta 2 glycoprotein I is a substrate of thiol oxidoreductases Passam, Freda H.; Rahgozar, Soheila; Qi, Miao Blood, Vol. 116, Issue 11 https://doi.org/10.1182/blood-2010-02-271494	journal	September 2010
Pulsed Interleaved Excitation Müller, Barbara K.; Zaychikov, Evgeny; Bräuchle, Christoph Biophysical Journal, Vol. 89, Issue 5 https://doi.org/10.1529/biophysj.105.064766	journal	November 2005
Regulators of complement activity mediate inhibitory mechanisms through a common C3b‐binding mode Forneris, Federico; Wu, Jin; Xue, Xiaoguang The EMBO Journal, Vol. 35, Issue 10 https://doi.org/10.15252/embj.201593673	journal	March 2016
Structural Architecture of Prothrombin in Solution Revealed by Single Molecule Spectroscopy Pozzi, Nicola; Bystranowska, Dominika; Zuo, Xiaobing Journal of Biological Chemistry, Vol. 291, Issue 35 https://doi.org/10.1074/jbc.M116.738310	journal	July 2016
Anti-phospholipid antibodies are directed against a complex antigen that includes a lipid-binding inhibitor of coagulation: beta 2-glycoprotein I (apolipoprotein H). McNeil, H. P.; Simpson, R. J.; Chesterman, C. N. Proceedings of the National Academy of Sciences, Vol. 87, Issue 11 https://doi.org/10.1073/pnas.87.11.4120	journal	June 1990
β2-Glycoprotein I can exist in 2 conformations: implications for our understanding of the antiphospholipid syndrome Ağar, Çetin; van Os, Gwendolyn M. A.; Mörgelin, Matthias Blood, Vol. 116, Issue 8 https://doi.org/10.1182/blood-2009-12-260976	journal	August 2010
Anticardiolipin antibodies (ACA) directed not to cardiolipin but to a plasma protein cofactor Galli, M.; Barbui, T.; Comfurius, P. The Lancet, Vol. 335, Issue 8705 https://doi.org/10.1016/0140-6736(90)91374-J	journal	June 1990
Plasmin Can Reduce the Function of Human β2Glycoprotein I by Cleaving Domain V Into a Nicked Form Ohkura, Naoki; Hagihara, Yoshihisa; Yoshimura, Tetsuro Blood, Vol. 91, Issue 11 https://doi.org/10.1182/blood.V91.11.4173	journal	June 1998
Proteolytic properties of single-chain factor XII: a mechanism for triggering contact activation Ivanov, Ivan; Matafonov, Anton; Sun, Mao-fu Blood, Vol. 129, Issue 11 https://doi.org/10.1182/blood-2016-10-744110	journal	March 2017
Single-Molecule FRET with Diffusion and Conformational Dynamics Gopich, Irina V.; Szabo, Attila The Journal of Physical Chemistry B, Vol. 111, Issue 44 https://doi.org/10.1021/jp075255e	journal	November 2007
Immune responses against domain I of β2-glycoprotein I are driven by conformational changes: Domain I of β2-glycoprotein I harbors a cryptic immunogenic epitope de Laat, Bas; van Berkel, Miranda; Urbanus, Rolf T. Arthritis & Rheumatism, Vol. 63, Issue 12 https://doi.org/10.1002/art.30633	journal	November 2011
β2-Glycoprotein I: evolution, structure and function: β2-Glycoprotein I De Groot, P. G.; Meijers, J. C. M. Journal of Thrombosis and Haemostasis, Vol. 9, Issue 7 https://doi.org/10.1111/j.1538-7836.2011.04327.x	journal	July 2011
Anti- 2 glycoprotein I ( 2GPI) autoantibodies recognize an epitope on the first domain of 2GPI Iverson, G. M.; Victoria, E. J.; Marquis, D. M. Proceedings of the National Academy of Sciences, Vol. 95, Issue 26 https://doi.org/10.1073/pnas.95.26.15542	journal	December 1998
Circulating β2 glycoprotein I-IgG anti-β2 glycoprotein I immunocomplexes in patients with definite Antiphospholipid Syndrome Banzato, A.; Frasson, R.; Acquasaliente, L. Lupus, Vol. 21, Issue 7 https://doi.org/10.1177/0961203312440347	journal	May 2012
Identification of a region of beta 2-glycoprotein I critical for lipid binding and anti-cardiolipin antibody cofactor activity. Hunt, J. E.; Simpson, R. J.; Krilis, S. A. Proceedings of the National Academy of Sciences, Vol. 90, Issue 6 https://doi.org/10.1073/pnas.90.6.2141	journal	March 1993
Determination of Domain Structure of Proteins from X-Ray Solution Scattering Svergun, Dmitri I.; Petoukhov, Maxim V.; Koch, Michel H. J. Biophysical Journal, Vol. 80, Issue 6 https://doi.org/10.1016/S0006-3495(01)76260-1	journal	June 2001
In Vivo Models of Thrombosis for the Antiphospholipid Syndrome Pierangeli, Ss; Harris, En Lupus, Vol. 5, Issue 5 https://doi.org/10.1177/096120339600500524	journal	October 1996
Annexin A2 mediates endothelial cell activation by antiphospholipid/anti-β2 glycoprotein I antibodies Zhang, Jianwei; McCrae, Keith R. Blood, Vol. 105, Issue 5 https://doi.org/10.1182/blood-2004-05-1708	journal	March 2005
β2-Glycoprotein I: a novel component of innate immunity Ağar, Çetin; de Groot, Philip G.; Mörgelin, Matthias Blood, Vol. 117, Issue 25 https://doi.org/10.1182/blood-2010-12-325951	journal	June 2011
Structure of Coagulation Factor II: Molecular Mechanism of Thrombin Generation and Development of Next-Generation Anticoagulants Chinnaraj, Mathivanan; Planer, William; Pozzi, Nicola Frontiers in Medicine, Vol. 5 https://doi.org/10.3389/fmed.2018.00281	journal	October 2018
Identification of the binding site for fondaparinux on Beta2-glycoprotein I Kolyada, Alexey; De Biasio, Alfredo; Beglova, Natalia Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, Vol. 1834, Issue 10 https://doi.org/10.1016/j.bbapap.2013.06.009	journal	October 2013
Antibodies to Domain I of β2Glycoprotein I are in close relation to patients risk categories in Antiphospholipid Syndrome (APS) Banzato, A.; Pozzi, N.; Frasson, R. Thrombosis Research, Vol. 128, Issue 6 https://doi.org/10.1016/j.thromres.2011.04.021	journal	December 2011
Lupus anticoagulant identifies two distinct groups of patients with different antibody patterns Pengo, V.; Del Ross, T.; Ruffatti, A. Thrombosis Research, Vol. 172 https://doi.org/10.1016/j.thromres.2018.11.003	journal	December 2018
New insight into antiphospholipid syndrome: antibodies to β2glycoprotein I-domain 5 fail to induce thrombi in rats Durigutto, Paolo; Grossi, Claudia; Borghi, Maria Orietta Haematologica, Vol. 104, Issue 4 https://doi.org/10.3324/haematol.2018.198119	journal	November 2018
Pathogenesis of antiphospholipid syndrome: understanding the antibodies Meroni, Pier Luigi; Borghi, M. Orietta; Raschi, Elena Nature Reviews Rheumatology, Vol. 7, Issue 6 https://doi.org/10.1038/nrrheum.2011.52	journal	May 2011
Dimers of β2-Glycoprotein I Increase Platelet Deposition to Collagen via Interaction with Phospholipids and the Apolipoprotein E Receptor 2′ Lutters, Bianca C. H.; Derksen, Ronald H. W. M.; Tekelenburg, Winnie L. Journal of Biological Chemistry, Vol. 278, Issue 36 https://doi.org/10.1074/jbc.M212655200	journal	September 2003
Patient-derived monoclonal antibodies directed towards beta2 glycoprotein-1 display lupus anticoagulant activity: Anti-β2GPI antibodies with LAC activity Dienava-Verdoold, I.; Boon-Spijker, M. G.; De Groot, P. G. Journal of Thrombosis and Haemostasis, Vol. 9, Issue 4 https://doi.org/10.1111/j.1538-7836.2011.04212.x	journal	April 2011
The X-ray Crystal Structure of Full-Length Human Plasminogen Law, Ruby H. P.; Caradoc-Davies, Tom; Cowieson, Nathan Cell Reports, Vol. 1, Issue 3 https://doi.org/10.1016/j.celrep.2012.02.012	journal	March 2012
Fluorescence-aided molecule sorting: Analysis of structure and interactions by alternating-laser excitation of single molecules Kapanidis, Achillefs N.; Lee, Nam Ki; Laurence, Ted A. Proceedings of the National Academy of Sciences, Vol. 101, Issue 24 https://doi.org/10.1073/pnas.0401690101	journal	June 2004
Molecular mapping of α-thrombin (αT)/β2-glycoprotein I (β2GpI) interaction reveals how β2GpI affects αT functions Acquasaliente, Laura; Peterle, Daniele; Tescari, Simone Biochemical Journal, Vol. 473, Issue 24 https://doi.org/10.1042/BCJ20160603	journal	December 2016
Coot model-building tools for molecular graphics Emsley, Paul; Cowtan, Kevin Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12, p. 2126-2132 https://doi.org/10.1107/S0907444904019158	journal	November 2004
Mechanism of the Interaction of β ₂ -Glycoprotein I with Negatively Charged Phospholipid Membranes ^† Hammel, Michal; Schwarzenbacher, Robert; Gries, Anna Biochemistry, Vol. 40, Issue 47 https://doi.org/10.1021/bi0114372	journal	November 2001
Lysine residues control the conformational dynamics of beta 2-glycoprotein I Buchholz, Ina; Nestler, Peter; Köppen, Susan Physical Chemistry Chemical Physics, Vol. 20, Issue 42 https://doi.org/10.1039/C8CP03234C	journal	January 2018
The Antiphospholipid Syndrome Levine, Jerrold S.; Branch, D. Ware; Rauch, Joyce New England Journal of Medicine, Vol. 346, Issue 10 https://doi.org/10.1056/NEJMra002974	journal	March 2002
A novel pathway for human endothelial cell activation by antiphospholipid/anti-β2 glycoprotein I antibodies Allen, Kristi L.; Fonseca, Fabio V.; Betapudi, Venkaiah Blood, Vol. 119, Issue 3 https://doi.org/10.1182/blood-2011-03-344671	journal	January 2012
Pathogenic anti-β2-glycoprotein I antibodies recognize domain I of β2-glycoprotein I only after a conformational change de Laat, Bas; Derksen, Ronald H. W. M.; van Lummel, Menno Blood, Vol. 107, Issue 5 https://doi.org/10.1182/blood-2005-05-1943	journal	March 2006
Lupus Anticoagulant Activity Is Frequently Dependent on the Presence of β2-Glycoprotein I Oostin, Janine D.; Derksen, Ronald H. W. M.; Entjes, H. Tanja I. Thrombosis and Haemostasis, Vol. 67, Issue 05 https://doi.org/10.1055/s-0038-1648480	journal	January 1992
[Anti-β2 Glycoprotein I—β2 Glycoprotein I] immune complexes in patients with antiphospholipid syndrome and other autoimmune diseases Biasiolo, A.; Rampazzo, P.; Brocco, T. Lupus, Vol. 8, Issue 2 https://doi.org/10.1191/096120399678847506	journal	February 1999
Shot-Noise Limited Single-Molecule FRET Histograms: Comparison between Theory and Experiments ^† Nir, Eyal; Michalet, Xavier; Hamadani, Kambiz M. The Journal of Physical Chemistry B, Vol. 110, Issue 44 https://doi.org/10.1021/jp063483n	journal	November 2006
Functional and structural insight into properdin control of complement alternative pathway amplification Pedersen, Dennis V.; Roumenina, Lubka; Jensen, Rasmus K. The EMBO Journal, Vol. 36, Issue 8 https://doi.org/10.15252/embj.201696173	journal	March 2017
Mode of Interaction between β2GPI and Lipoprotein Receptors Suggests Mutually Exclusive Binding of β2GPI to the Receptors and Anionic Phospholipids Lee, Chang-Jin; De Biasio, Alfredo; Beglova, Natalia Structure, Vol. 18, Issue 3 https://doi.org/10.1016/j.str.2009.12.013	journal	March 2010
Structure of prothrombin in the closed form reveals new details on the mechanism of activation Chinnaraj, Mathivanan; Chen, Zhiwei; Pelc, Leslie A. Scientific Reports, Vol. 8, Issue 1 https://doi.org/10.1038/s41598-018-21304-1	journal	February 2018
Use of Single Point Mutations in Domain I of β ₂ -Glycoprotein I to Determine Fine Antigenic Specificity of Antiphospholipid Autoantibodies Iverson, G. Michael; Reddel, Stephen; Victoria, Edward J. The Journal of Immunology, Vol. 169, Issue 12 https://doi.org/10.4049/jimmunol.169.12.7097	journal	December 2002
Solution Structure of Human and Bovine β2-Glycoprotein I Revealed by Small-angle X-ray Scattering Hammel, Michal; Kriechbaum, Manfred; Gries, Anna Journal of Molecular Biology, Vol. 321, Issue 1 https://doi.org/10.1016/S0022-2836(02)00621-6	journal	August 2002
A practical guide to small angle X-ray scattering (SAXS) of flexible and intrinsically disordered proteins Kikhney, Alexey G.; Svergun, Dmitri I. FEBS Letters, Vol. 589, Issue 19PartA https://doi.org/10.1016/j.febslet.2015.08.027	journal	August 2015
Induction of anti-β2-glycoprotein I autoantibodies in mice by protein H of Streptococcus pyogenes: Induction of anti-β2-GPI autoantibodies Van Os, G. M. A.; Meijers, J. C. M.; Agar, Ç. Journal of Thrombosis and Haemostasis, Vol. 9, Issue 12 https://doi.org/10.1111/j.1538-7836.2011.04532.x	journal	December 2011
Novel assays of thrombogenic pathogenicity in the antiphospholipid syndrome based on the detection of molecular oxidative modification of the major autoantigen β ₂ ‐glycoprotein I Ioannou, Yiannis; Zhang, Jing‐Yun; Qi, Miao Arthritis & Rheumatism, Vol. 63, Issue 9 https://doi.org/10.1002/art.30383	journal	August 2011
[20] Processing of X-ray diffraction data collected in oscillation mode Otwinowski, Zbyszek; Minor, Wladek Macromolecular Crystallography Part A, 307-326 https://doi.org/10.1016/S0076-6879(97)76066-X	book	January 1997
�ber ein bisher unbekanntes niedermolekulares ?2-Glubulin des Humanserums Schultze, H. E.; Heide, K.; Haupt, H. Die Naturwissenschaften, Vol. 48, Issue 23 https://doi.org/10.1007/BF00620967	journal	January 1961
Thrombus formation induced by antibodies to β2-glycoprotein I is complement dependent and requires a priming factor Fischetti, Fabio; Durigutto, Paolo; Pellis, Valentina Blood, Vol. 106, Issue 7 https://doi.org/10.1182/blood-2005-03-1319	journal	October 2005

Similar Records

An allosteric redox switch in domain V of β2-glycoprotein I controls membrane binding and anti-domain I autoantibody recognition

Journal Article · Sun Aug 01 00:00:00 EDT 2021 · Journal of Biological Chemistry · OSTI ID:1772485

Kumar, Suresh; Chinnaraj, Mathivanan; Planer, William; +4 more

A Novel Dimeric Inhibitor Targeting Beta2GPI in Beta2GPI/Antibody Complexes Implicated in Antiphospholipid Syndrome

Journal Article · Sat Dec 31 00:00:00 EST 2011 · PLoS One · OSTI ID:1772485

Kolyada, A; Lee, C; Biasio, A De; +1 more

A Novel Dimeric Inhibitor Targeting Beta2GPI in Beta2GPI/Antibody Complexes Implicated in Antiphospholipid Syndrome

Journal Article · Wed Dec 15 00:00:00 EST 2010 · PLoS ONE · OSTI ID:1772485

Kolyada, Alexey; Lee, Chang-Jin; De Biasio, Alfredo; +1 more

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
BioSAXS
X-ray crystallography
antiphospholipid syndrome
autoimmune disease
autoimmunity
thrombosis
beta-2 glycoprotein I
coagulation
complement system
lipid-protein interaction
protein-protein interaction
single-molecule biophysics
structural biology
structure-function

Title: The J-elongated conformation of β2-glycoprotein I predominates in solution: Implications for our understanding of antiphospholipid syndrome

Citation Formats

References (71)

Similar Records

Related Subjects

Title: The J-elongated conformation of β₂-glycoprotein I predominates in solution: Implications for our understanding of antiphospholipid syndrome