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Characterization of αX I-Domain Binding to Receptors for Advanced Glycation End Products (RAGE)

  • Buyannemekh, Dolgorsuren (Divisions of Science Education and Biology, Kangwon National University) ;
  • Nham, Sang-Uk (Divisions of Science Education and Biology, Kangwon National University)
  • Received : 2017.02.10
  • Accepted : 2017.04.27
  • Published : 2017.05.31

Abstract

The ${\beta}2$ integrins are cell surface transmembrane proteins regulating leukocyte functions, such as adhesion and migration. Two members of ${\beta}2$ integrin, ${\alpha}M{\beta}2$ and ${\alpha}X{\beta}2$, share the leukocyte distribution profile and integrin ${\alpha}X{\beta}2$ is involved in antigen presentation in dendritic cells and transendothelial migration of monocytes and macrophages to atherosclerotic lesions. ${\underline{R}}eceptor$ for ${\underline{a}}dvanced$ ${\underline{g}}lycation$ ${\underline{e}}nd$ ${\underline{p}}roducts$ (RAGE), a member of cell adhesion molecules, plays an important role in chronic inflammation and atherosclerosis. Although RAGE and ${\alpha}X{\beta}2$ play an important role in inflammatory response and the pathogenesis of atherosclerosis, the nature of their interaction and structure involved in the binding remain poorly defined. In this study, using I-domain as a ligand binding motif of ${\alpha}X{\beta}2$, we characterize the binding nature and the interacting moieties of ${\alpha}X$ I-domain and RAGE. Their binding requires divalent cations ($Mg^{2+}$ and $Mn^{2+}$) and shows an affinity on the sub-micro molar level: the dissociation constant of ${\alpha}X$ I-domains binding to RAGE being $0.49{\mu}M$. Furthermore, the ${\alpha}X$ I-domains recognize the V-domain, but not the C1 and C2-domains of RAGE. The acidic amino acid substitutions on the ligand binding site of ${\alpha}X$ I-domain significantly reduce the I-domain binding activity to soluble RAGE and the alanine substitutions of basic amino acids on the flat surface of the V-domain prevent the V-domain binding to ${\alpha}X$ I-domain. In conclusion, the main mechanism of ${\alpha}X$ I-domain binding to RAGE is a charge interaction, in which the acidic moieties of ${\alpha}X$ I-domains, including E244, and D249, recognize the basic residues on the RAGE V-domain encompassing K39, K43, K44, R104, and K107.

Acknowledgement

Supported by : Kangwon National University

References

  1. Arnaout, M.A. (2002). Integrin structure: new twists and turns in dynamic cell adhesion, Immunol. Rev. 186, 125-140. https://doi.org/10.1034/j.1600-065X.2002.18612.x
  2. Baker, N.A., Sept, D., Joseph, S., Holst, M.J., and McCammon, J.A. (2001). Electrostatics of nanosystems: application to microtubules and the ribosome. Proc. Natl. Acad. Sci. USA 98, 10037-10041. https://doi.org/10.1073/pnas.181342398
  3. Chavakis, T., Bierhaus, A., Al-Fakhri, N., Schneider, D., Witte, S., Linn, T., Nagashima, M., Morser, J., Arnold, B., Preissner, K.T., et al. (2003). The pattern recognition receptor (RAGE) is a counterreceptor for leukocyte integrins: a novel pathway for inflammatory cell recruitment. J. Exp. Med. 198, 1507-1515. https://doi.org/10.1084/jem.20030800
  4. Choi, J., Leyton, L., and Nham, S.-U. (2005). Characterization of ${\alpha}$X Idomain binding to Thy-1. Biochem. Biophy. Res. Comm. 331, 557-561. https://doi.org/10.1016/j.bbrc.2005.04.006
  5. Choi, J., Choi, J., and Nham, S.-U. (2010). Characterization of the residues of ${\alpha}$X I-domain and ICAM-1 mediating their interactions. Mol. Cells 30, 227-234. https://doi.org/10.1007/s10059-010-0111-2
  6. Deane, R., Yan, S.D., Submamaryan, R.K., LaRue, B., Jovanovic, S., Hogg, E., Welch, D., Manness, L., Lin, C., Yu, J., et al. (2003). RAGE mediates amyloid-beta peptide transport across the blood-brain barrier and accumulation in brain. Nat. Med. 9, 907-913. https://doi.org/10.1038/nm890
  7. Foster, G.A., Xu, L., Chidambaram, A.A., Soderberg, S.R., Armstrong, E.J., Wu, H., and Simon, S.I. (2015). CD11c/CD18 signals Very Late Antigen-4 activation to initiate foamy monocyte recruitment during the onset of hypercholesterolemia. J. Immunol.195, 5380-5392. https://doi.org/10.4049/jimmunol.1501077
  8. Frommhold, D., Kamphues,A., Hepper, I., Pruenster, M., Lukic, I.K., Socher, I., Zablotskaya, V., Buschmann, K., Lange-Sperandio, B., Schymeinsky, J., et al. (2010). RAGE and ICAM-1 cooperate in mediating leukocyte recruitment during acute inflammation in vivo. Blood 116, 841-849. https://doi.org/10.1182/blood-2009-09-244293
  9. Gang, J., Choi, J., Lee, J.H., and Nham, S.-U. (2007). Identification of critical residues for plasminogen binding by the ${\alpha}$X I-domain of the ${\beta}$2 integrin, ${\alpha}$X${\beta}$2, Mol. Cells 24, 240-246.
  10. Higgins, D.R. (1995). Heterologous protein expression in the methylotrophic yeast Pichia pastoris, in: J.E. Coligan, B.M. Dunn, H.L. Ploegh, D.W. Speicher, P.T. Wingfield., eds., (Current protocols in protein science, John Wiley & Sons, Inc.), pp. 5.7.1-5.7.16.
  11. Hofmann, M.A., Drury, S., Fu, C., Qu, W., Taguchi, A., Lu, Y., Avila, C., Kambham, N., Bierhaus, A., Nawroth, P., et al. (1999). RAGE mediates a novel proinflammatory axis: a central cell surface receptor for S100/calgranulin polypeptides. Cell 97, 889-901. https://doi.org/10.1016/S0092-8674(00)80801-6
  12. Hogg, N., Takacs, L., Palmer, D.G., Selvendran, Y., and Allen, C. (1986). The p150,95 molecule is a marker of human mononuclear phagocytes: comparison with expression of class II molecules. Eur. J. Immunol. 16, 240-248. https://doi.org/10.1002/eji.1830160306
  13. Hori, O., Brett, J., Slattery, T., Cao, R., Zhang, J., Chen, J.X., Nagashima, M., Lundh, E.R., Vijay, S., Nitecki, D., et al. (1995). The receptor for advanced glycation end products (RAGE) is a cellular binding site for amphoterin. J. Biol. Chem. 270, 25752-25761. https://doi.org/10.1074/jbc.270.43.25752
  14. Hynes, R.O. (2002). Integrins: bidirectional, allosteric signaling machines. Cell 110, 673-687. https://doi.org/10.1016/S0092-8674(02)00971-6
  15. Kierdorf, K., and Fritz, G. (2013). RAGE regulation and signaling in inflammation and beyond. J. Leukoc. Biol. 94, 55-68. https://doi.org/10.1189/jlb.1012519
  16. Koch, M., Chitayat, S., Dattilo, B.M., Schiefner, A., Diez, J., Chazin, W.J., and Fritz, G. (2010). Structural basis for ligand recognition and activation of RAGE. Structure 18, 1342-1352. https://doi.org/10.1016/j.str.2010.05.017
  17. Korndorfer, I. P., Brueckner, F., and Skerra, A. (2007). The crystal structure of the human (S100A8/S100A9)2 heterotetramer, calprotectin, illustrates how conformational changes of interacting alpha-helices can determine specific association of two EF-hand proteins. J. Mol. Biol. 370, 887-898. https://doi.org/10.1016/j.jmb.2007.04.065
  18. Leclerc, E., Fritz, G., Weibel, M., Heizmann, C.W., and Galichet, A. (2007). S100B and S100A6 differentially modulate cell survival by interacting with distinct RAGE (receptor for advanced glycation end products) immunoglobulin domains. J. Biol. Chem. 282, 31317-31331. https://doi.org/10.1074/jbc.M703951200
  19. Lee, J.O., Rieu, P., Arnaout, M.A., and Liddington, R.C. (1995). Crystal structure of the A domain from the ${\alpha}$ subunit of integrin CR3 (CD11b/CD18). Cell 80, 631-638. https://doi.org/10.1016/0092-8674(95)90517-0
  20. Lee, J.H., Choi, J., and Nham, S.-U. (2007). Critical residues of ${\alpha}$X Idomain recognizing fibrinogen central domain. Biochem. Biophys. Res. Comm. 355, 1058-1063. https://doi.org/10.1016/j.bbrc.2007.02.082
  21. Luo, B.-H., Carman, C.V., and Springer, T.A. (2007). Structural basis of integrin regulation and signaling. Annu. Rev. Immunol. 25, 619-647 https://doi.org/10.1146/annurev.immunol.25.022106.141618
  22. Matsumoto, S., Yoshida,T., Murata, H., Harada, S., Fujita, N., Nakamura, S., Yamamoto, Y., Watanabe, T., Yonekura, H., Yamamoto, H., et al. (2008). Solution structure of the variable-type domain of the receptor for advanced glycation end products: new insight into AGE-RAGE interaction. Biochemistry 47, 12299-12311. https://doi.org/10.1021/bi800910v
  23. Meunier, L., Bohjanen, K., Voorhees, J.J., and Cooper, K.D. (1994). Retinoic acid upregulates human Langerhans cell antigen presentation and surface expression of HLA-DR and CD11c, a ${\beta}$2 integrin critically involved in T-cell activation. J. Invest. Dermatol. 103, 775-779. https://doi.org/10.1111/1523-1747.ep12413014
  24. Pettersen, E.F., Goddard, T.D., Huang, C.C., Couch, G.S., Greenblatt, D.M., Meng, E.C., and Ferrin, T.E. (2004). UCSF Chimera-a visualization system for exploratory research and analysis. J. Comput. Chem. 25, 1605-1612. https://doi.org/10.1002/jcc.20084
  25. Sambrook, J., and Russell, D.W. (2001). Purification of histidinetagged proteins by immobilized $Ni^{2+}$ absorption chromatography, in: Molecular Cloning, a laboratory manual, (Cold Spring Harbor Laboratory Press, New York), pp. 15.44-15.48.
  26. Sims, G.P., Rowe, D.C., Rietdijk, S.T., Herbst, R., and Coyle, A.J. (2010). HMGB1 and RAGE in inflammation and cancer. Annu. Rev. Immunol. 28, 367-388. https://doi.org/10.1146/annurev.immunol.021908.132603
  27. Sousa, M.M., Yan, S.D., Stern, D., and Saraiva, J.M. (2000). Interaction of the receptor for advanced glycation end products (RAGE) with transthyretin triggers nuclear transcription factor kB (NFkB) activation. Lab. Invest. 80, 1101-1110. https://doi.org/10.1038/labinvest.3780116
  28. Stacker, S.A., and Springer, T.A. (1991). Leukocyte integrin P150,95 (CD11c/CD18) functions as an adhesion molecule binding to a counter-receptor on stimulated endothelium. J. Immunol. 146, 648-655.
  29. Sturchler, E., Galichet, A., Weibel, M., Leclerc, E., and Heizmann, C.W. (2008). Site-specific blockade of RAGE-Vd prevents amyloid-${\beta}$oligomer neurotoxicity. J. Neurosci. 28, 5149-5158. https://doi.org/10.1523/JNEUROSCI.4878-07.2008
  30. Tan, S. M. (2012). The leucocyte ${\beta}$2 (CD18) integrins: the structure, functional regulation and signaling properties. Biosci. Rep. 32, 241-269. https://doi.org/10.1042/BSR20110101
  31. Vorup-Jensen, T., Ostermeier, C., Shimaoka, M., Hommel, U., and Springer, T.A. (2003). Structure and allosteric regulation of the ${\alpha}$X${\beta}$2 integrin I-domain. Proc. Natl. Acad. Sci. USA 100, 1873-1878. https://doi.org/10.1073/pnas.0237387100
  32. Vorup-Jensen, T., Carman, C.V., Shimaoka, M., Schuck, P., Svitel, J., and Springer, T.A. (2005). Exposure of acidic residues as a danger signal for recognition of fibrinogen and other macromolecules by integrin ${\alpha}$X${\beta}$2. Proc. Natl. Acad. Sci. U S A. 102, 1614-1619. https://doi.org/10.1073/pnas.0409057102
  33. Wu, H., Gower, R.M., Wang, H., Perrard, X.-Y., Ma, R., Bullard, D.C., Burns, A.R., Paul, A., Smith, C.W., Simon, S.I., et al. (2009). Functional role of $CD11c^+$ monocytes in atherogenesis associated with hypercholesterolemia. Circulation 119, 2708-2717. https://doi.org/10.1161/CIRCULATIONAHA.108.823740
  34. Xiong, J.P., Li, R., Essafi, M., Stehle, T., and Arnaout, M.A. (2000). An isoleucine-based allosteric switch controls affinity and shape shifting in integrin CD11b A-domain. J. Biol. Chem. 275, 38762-38768. https://doi.org/10.1074/jbc.C000563200
  35. Zen, K., Chen, C.X., Chen, Y.T., Wilton, R., and Liu, Y. (2007). Receptor for advanced glycation endproducts mediates neutrophil migration across intestinal epithelium. J. Immunol. 178, 2483-2490. https://doi.org/10.4049/jimmunol.178.4.2483
  36. Zieman, S.J., and Kass, D.A. (2004). Advanced glycation endproduct crosslinking in the cardiovascular system: potential therapeutic target for cardiovascular disease. Drugs 64, 459-470. https://doi.org/10.2165/00003495-200464050-00001