Structural Insights into Recognition of Beta2-glycoprotein I by the Lipoprotein Receptors

Overview

Journal Proteins

Date 2009 Aug 14

PMID 19676115

Citations 6

Authors

Dmitri Beglov

Chang-Jin Lee

Alfredo De Biasio

Dima Kozakov

Ryan Brenke

Sandor Vajda

Natalia Beglova

Affiliations

Soon will be listed here.

Abstract

The interactions of beta2 glycoprotein I (B2GPI) with the receptors of the low-density lipoprotein receptor (LDLR) family are implicated in the clearance of negatively charged phospholipids and apoptotic cells and, in the presence of autoimmune anti-B2GPI antibodies, in cell activation, which might play a role in the pathology of antiphospholipid syndrome (APS). The ligand-binding domains of the lipoprotein receptors consist of multiple homologous LA modules connected by flexible linkers. In this study, we investigated at the atomic level the features of the LA modules required for binding to B2GPI. To compare the binding interface in B2GPI/LA complex to that observed in the high-resolution co-crystal structure of the receptor associated protein (RAP) with a pair of LA modules 3 and 4 from the LDLR, we used LA4 in our studies. Using solution NMR spectroscopy, we found that LA4 interacts with B2GPI and the binding site for B2GPI on the (15)N-labeled LA4 is formed by the calcium coordinating residues of the LA module. We built a model for the complex between domain V of B2GPI (B2GPI-DV) and LA4 without introducing any experimentally derived constraints into the docking procedure. Our model, which is in the agreement with the NMR data, suggests that the binding interface of B2GPI for the lipoprotein receptors is centered at three lysine residues of B2GPI-DV, Lys 308, Lys 282, and Lys317.

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References

Estrada K, Fisher C, Blacklow S . Unfolding of the RAP-D3 helical bundle facilitates dissociation of RAP-receptor complexes. Biochemistry. 2008; 47(6):1532-9. DOI: 10.1021/bi702076y. View

Fisher C, Beglova N, Blacklow S . Structure of an LDLR-RAP complex reveals a general mode for ligand recognition by lipoprotein receptors. Mol Cell. 2006; 22(2):277-83. DOI: 10.1016/j.molcel.2006.02.021. View

Pennings M, Derksen R, van Lummel M, Adelmeijer J, Vanhoorelbeke K, Urbanus R . Platelet adhesion to dimeric beta-glycoprotein I under conditions of flow is mediated by at least two receptors: glycoprotein Ibalpha and apolipoprotein E receptor 2'. J Thromb Haemost. 2006; 5(2):369-77. DOI: 10.1111/j.1538-7836.2007.02310.x. View

Jensen G, Andersen O, Bonvin A, Bjerrum-Bohr I, Etzerodt M, Thogersen H . Binding site structure of one LRP-RAP complex: implications for a common ligand-receptor binding motif. J Mol Biol. 2006; 362(4):700-16. DOI: 10.1016/j.jmb.2006.07.013. View

Verdaguer N, Fita I, Reithmayer M, Moser R, Blaas D . X-ray structure of a minor group human rhinovirus bound to a fragment of its cellular receptor protein. Nat Struct Mol Biol. 2004; 11(5):429-34. DOI: 10.1038/nsmb753. View

Pons J, Malliavin T, Delsuc M . Gifa V. 4: A complete package for NMR data set processing. J Biomol NMR. 2010; 8(4):445-52. DOI: 10.1007/BF00228146. View

Shen Y, Brenke R, Kozakov D, Comeau S, Beglov D, Vajda S . Docking with PIPER and refinement with SDU in rounds 6-11 of CAPRI. Proteins. 2007; 69(4):734-42. DOI: 10.1002/prot.21754. View

Jeon H, Blacklow S . Structure and physiologic function of the low-density lipoprotein receptor. Annu Rev Biochem. 2005; 74:535-62. DOI: 10.1146/annurev.biochem.74.082803.133354. View

Pennings M, Derksen R, Urbanus R, Tekelenburg W, Hemrika W, de Groot P . Platelets express three different splice variants of ApoER2 that are all involved in signaling. J Thromb Haemost. 2007; 5(7):1538-44. DOI: 10.1111/j.1538-7836.2007.02605.x. View

10.

Lutters B, Derksen R, Tekelenburg W, Lenting P, Arnout J, de Groot P . Dimers of beta 2-glycoprotein I increase platelet deposition to collagen via interaction with phospholipids and the apolipoprotein E receptor 2'. J Biol Chem. 2003; 278(36):33831-8. DOI: 10.1074/jbc.M212655200. View

11.

van Lummel M, Pennings M, Derksen R, Urbanus R, Lutters B, Kaldenhoven N . The binding site in {beta}2-glycoprotein I for ApoER2' on platelets is located in domain V. J Biol Chem. 2005; 280(44):36729-36. DOI: 10.1074/jbc.M504172200. View

12.

Rudenko G, Henry L, Henderson K, Ichtchenko K, Brown M, Goldstein J . Structure of the LDL receptor extracellular domain at endosomal pH. Science. 2002; 298(5602):2353-8. DOI: 10.1126/science.1078124. View

13.

. The CCP4 suite: programs for protein crystallography. Acta Crystallogr D Biol Crystallogr. 1994; 50(Pt 5):760-3. DOI: 10.1107/S0907444994003112. View

14.

North C, Blacklow S . Solution structure of the sixth LDL-A module of the LDL receptor. Biochemistry. 2000; 39(10):2564-71. DOI: 10.1021/bi992087a. View

15.

Bouma B, de Groot P, van den Elsen J, Ravelli R, Schouten A, Simmelink M . Adhesion mechanism of human beta(2)-glycoprotein I to phospholipids based on its crystal structure. EMBO J. 1999; 18(19):5166-74. PMC: 1171587. DOI: 10.1093/emboj/18.19.5166. View

16.

Beglova N, North C, Blacklow S . Backbone dynamics of a module pair from the ligand-binding domain of the LDL receptor. Biochemistry. 2001; 40(9):2808-15. DOI: 10.1021/bi0027276. View

17.

Fass D, Blacklow S, Kim P, Berger J . Molecular basis of familial hypercholesterolaemia from structure of LDL receptor module. Nature. 1997; 388(6643):691-3. DOI: 10.1038/41798. View

18.

Andersen O, Christensen P, Christensen L, Jacobsen C, Moestrup S, Etzerodt M . Specific binding of alpha-macroglobulin to complement-type repeat CR4 of the low-density lipoprotein receptor-related protein. Biochemistry. 2000; 39(35):10627-33. DOI: 10.1021/bi000498h. View

19.

Mehdi H, Naqvi A, Kamboh M . A hydrophobic sequence at position 313-316 (Leu-Ala-Phe-Trp) in the fifth domain of apolipoprotein H (beta2-glycoprotein I) is crucial for cardiolipin binding. Eur J Biochem. 2000; 267(6):1770-6. DOI: 10.1046/j.1432-1327.2000.01174.x. View

20.

Dolmer K, Huang W, Gettins P . NMR solution structure of complement-like repeat CR3 from the low density lipoprotein receptor-related protein. Evidence for specific binding to the receptor binding domain of human alpha(2)-macroglobulin. J Biol Chem. 2000; 275(5):3264-9. DOI: 10.1074/jbc.275.5.3264. View