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Lipoprotein(a) Binds to C-terminal Lysine Residues of Recombinant Enolase Derived from Group A Streptococcus

Received: 3 December 2015     Published: 4 December 2015
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Abstract

The biological function of lipoprotein(a) [Lp(a)] remains elusive although it was identified in 1963. We previously hypothesized that Lp(a) might inhibit pathogens from hijacking host plasminogen (Plg) since apolipoprotein(a) [Apo(a)], a unique protein in Lp(a), shares a high homology with Plg. We demonstrate that Lp(a) bound to recombinant Streptococcal α-enolase (rSEN), which is a surface Plg receptor on group A Streptococcus (GAS). However, recombinant C-terminal lysines-deleted variant of enolase (rSENΔ434-435) did not bind to Lp(a). Moreover, epsilon-aminocaproic acid (EACA), a lysine analog, significantly inhibited the binding of rSEN to Lp(a). Collectively, Lp(a) via its LBS bound to the C-terminal lysines of rSEN. In addition, Lp(a) only competitively blocked the Plg-rSEN interaction but not Plg-rSENΔ434-435 interaction since Plg could also bind to the internal lysine residue of α-enolase. The preliminary study indicated that Lp(a) also interacted with GAS, consequently competitively inhibiting the Plg-GAS binding to some extent. Therefore, Lp(a) might play a limited role in preventing GAS infection since it only partially inhibited the pathogen from recruiting host Plg.

Published in American Journal of Clinical and Experimental Medicine (Volume 3, Issue 5)
DOI 10.11648/j.ajcem.20150305.33
Page(s) 327-331
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2015. Published by Science Publishing Group

Keywords

Lipoprotein(a), Group A Streptococcus, Plasminogen, α-Enolase

References
[1] A. H. Nobbs, R. J. Lamont, H. F. Jenkinson. Streptococcus Adherence and Colonization. Microbiol. Mol. Biol. Rev., 2009, 73: 407-450.
[2] A. Berge, U. Sjobring. PAM, a novel plasminogen-binding protein from Streptococcus pyogenes. J. Biol. Chem., 1993, 268: 25417-25424.
[3] V. Pancholi, V. A. Fischetti. alpha-enolase, a novel strong plasmin(ogen) binding protein on the surface of pathogenic streptococci. J. Biol. Chem., 1998, 273: 14503-14515.
[4] M. J. Walker, J. D. Mcarthur, F. Mckay, et al. Is plasminogen deployed as a Streptococcus pyogenes virulence factor? Trends Microbiol., 2005, 13: 308-313.
[5] M. L. Sanderson-Smith, D. M. P. De Oliveira, M. Ranson, et al. Bacterial Plasminogen Receptors: Mediators of a Multifaceted Relationship. J. Biomed. Biotechnol., 2012.
[6] S. Bhattacharya, V. A. Ploplis, F. J. Castellino. Bacterial Plasminogen Receptors Utilize Host Plasminogen System for Effective Invasion and Dissemination. J. Biomed. Biotechnol., 2012.
[7] A. J. Cork, S. Jergic, S. Hammerschmidt, et al. Defining the Structural Basis of Human Plasminogen Binding by Streptococcal Surface Enolase. J. Biol. Chem., 2009, 284: 17129-17137.
[8] E. Anuurad, M. B. Boffa, M. L. Koschinsky, et al. Lipoprotein(a): A unique risk factor for cardiovascular disease. Clin. Lab. Med., 2006, 26: 751-+.
[9] L. Berglund, R. Ramakrishnan. Lipoprotein(a): An elusive cardiovascular risk factor. Arterioscler. Thromb. Vasc. Biol., 2004, 24: 2219-2226.
[10] M. L. Koschinsky. Novel insights into Lp(a) physiology and pathogenicity: more questions than answers? Cardiovasc. Hematol. Disord. Drug Targets, 2006, 6: 267-278.
[11] S. P. A. Mccormick. Lipoprotein(a): biology and clinical importance. Clin. Biochem. Reviews/AACB, 2004, 25: 69-80.
[12] J. W. Mclean, J. E. Tomlinson, W. J. Kuang, et al. cDNA sequence of human apolipoprotein(a) is homologous to plasminogen. Nature, 1987, 330: 132-137.
[13] M. N. Rahman, V. Petrounevitch, Z. Jia, et al. Antifibrinolytic effect of single apo(a) kringle domains: relationship to fibrinogen binding. Protein Eng., 2001, 14: 427-438.
[14] S. Agarwal, P. Kulshreshtha, D. B. Mukku, et al. alpha-Enolase binds to human plasminogen on the surface of Bacillus anthracis. BBA-Proteins Proteomics, 2008, 1784: 986-994.
[15] V. Chumchua, N. Pornputtapong, C. Thammarongtham, et al. Homology modeling of Mycoplasma pneumoniae enolase and its molecular interaction with human plasminogen. Bioinformation, 2008, 3: 18-23.
[16] M. C. Jobin, J. Brassard, S. Quessy, et al. Acquisition of host plasmin activity by the swine pathogen Streptococcus suis serotype 2. Infect. Immun., 2004, 72: 606-610.
[17] K. Lahteenmaki, P. Kuusela, T. K. Korhonen. Bacterial plasminogen activators and receptors. FEMS Microbiol. Rev., 2001, 25: 531-552.
[18] J. Sha, T. E. Erova, R. A. Alyea, et al. Surface-Expressed Enolase Contributes to the Pathogenesis of Clinical Isolate SSU of Aeromonas hydrophila. J. Bacteriol., 2009, 191: 3095-3107.
[19] V. Mundodi, A. S. Kucknoor, J. F. Alderete. Immunogenic and plasminogen-binding surface-associated alpha-enolase of Trichomonas vaginalis. Infect. Immun., 2008, 76: 523-531.
[20] A. Ramajo-Hernandez, R. Perez-Sanchez, V. Ramajo-Martin, et al. Schistosoma bovis: Plasminogen binding in adults and the identification of plasminogen-binding proteins from the worm tegument. Exp. Parasitol., 2007, 115: 83-91.
[21] M. Rojas, I. Labrador, J. L. Concepcion, et al. Characteristics of plasminogen binding to Trypanosoma cruzi epimastigotes. Acta Trop., 2008, 107: 54-58.
[22] G. Vanegas, W. Quinones, C. Carrasco-Lopez, et al. Enolase as a plasminogen binding protein in Leishmania mexicana. Parasitol. Res., 2007, 101: 1511-1516.
[23] J. D. Crowe, I. K. Sievwright, G. C. Auld, et al. Candida albicans binds human plasminogen: identification of eight plasminogen-binding proteins. Mol. Microbiol., 2003, 47: 1637-1651.
[24] H. M. Sun, U. Ringdahl, J. W. Homeister, et al. Plasminogen is a critical host pathogenicity factor for group A streptococcal infection. Science, 2004, 305: 1283-1286.
[25] A. Godier, B. J. Hunt. Plasminogen receptors and their role in the pathogenesis of inflammatory, autoimmune and malignant disease. J. Thromb. Haemost., 2013, 11: 26-34.
[26] R. Romagnuolo, K. Demarco, M. B. Boffa, et al. Apolipoprotein(a) inhibits the conversion of Glu-plasminogen to Lys-plasminogen on the surface of vascular endothelial and smooth muscle cells. J. Thromb. Haemost., 2013, 11: 377-377.
[27] X. Y. Dai, L. P. Xu, W. C. Bai, et al. The interaction between lipoprotein(a) anrecombinant glyceraldehyde-3-phosphate dehudrogenase derived from group a streptococcus (in Chinese). J. Inner Mongolia Agric. Univ., 2011, 32: 27-31.
[28] R. Romagnuolo, S. M. Marcovina, M. B. Boffa, et al. Inhibition of plasminogen activation by apo(a): role of carboxyl-terminal lysines and identification of inhibitory domains in apo(a). J. Lipid Res., 2014, 55: 625-634.
[29] R. L. Han. Plasma lipoproteins are important components of the immune system. Microbiol. Immunol., 2010, 54: 246-253.
Cite This Article
  • APA Style

    Liping Xu, Wencheng Bai, Zhixing Ji, Xiaoyan Dai, Yun Pang, et al. (2015). Lipoprotein(a) Binds to C-terminal Lysine Residues of Recombinant Enolase Derived from Group A Streptococcus. American Journal of Clinical and Experimental Medicine, 3(5), 327-331. https://doi.org/10.11648/j.ajcem.20150305.33

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    ACS Style

    Liping Xu; Wencheng Bai; Zhixing Ji; Xiaoyan Dai; Yun Pang, et al. Lipoprotein(a) Binds to C-terminal Lysine Residues of Recombinant Enolase Derived from Group A Streptococcus. Am. J. Clin. Exp. Med. 2015, 3(5), 327-331. doi: 10.11648/j.ajcem.20150305.33

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    AMA Style

    Liping Xu, Wencheng Bai, Zhixing Ji, Xiaoyan Dai, Yun Pang, et al. Lipoprotein(a) Binds to C-terminal Lysine Residues of Recombinant Enolase Derived from Group A Streptococcus. Am J Clin Exp Med. 2015;3(5):327-331. doi: 10.11648/j.ajcem.20150305.33

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  • @article{10.11648/j.ajcem.20150305.33,
      author = {Liping Xu and Wencheng Bai and Zhixing Ji and Xiaoyan Dai and Yun Pang and Feng Huo and Wenlong Li and Runlin Han},
      title = {Lipoprotein(a) Binds to C-terminal Lysine Residues of Recombinant Enolase Derived from Group A Streptococcus},
      journal = {American Journal of Clinical and Experimental Medicine},
      volume = {3},
      number = {5},
      pages = {327-331},
      doi = {10.11648/j.ajcem.20150305.33},
      url = {https://doi.org/10.11648/j.ajcem.20150305.33},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajcem.20150305.33},
      abstract = {The biological function of lipoprotein(a) [Lp(a)] remains elusive although it was identified in 1963. We previously hypothesized that Lp(a) might inhibit pathogens from hijacking host plasminogen (Plg) since apolipoprotein(a) [Apo(a)], a unique protein in Lp(a), shares a high homology with Plg. We demonstrate that Lp(a) bound to recombinant Streptococcal α-enolase (rSEN), which is a surface Plg receptor on group A Streptococcus (GAS). However, recombinant C-terminal lysines-deleted variant of enolase (rSENΔ434-435) did not bind to Lp(a). Moreover, epsilon-aminocaproic acid (EACA), a lysine analog, significantly inhibited the binding of rSEN to Lp(a). Collectively, Lp(a) via its LBS bound to the C-terminal lysines of rSEN. In addition, Lp(a) only competitively blocked the Plg-rSEN interaction but not Plg-rSENΔ434-435 interaction since Plg could also bind to the internal lysine residue of α-enolase. The preliminary study indicated that Lp(a) also interacted with GAS, consequently competitively inhibiting the Plg-GAS binding to some extent. Therefore, Lp(a) might play a limited role in preventing GAS infection since it only partially inhibited the pathogen from recruiting host Plg.},
     year = {2015}
    }
    

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  • TY  - JOUR
    T1  - Lipoprotein(a) Binds to C-terminal Lysine Residues of Recombinant Enolase Derived from Group A Streptococcus
    AU  - Liping Xu
    AU  - Wencheng Bai
    AU  - Zhixing Ji
    AU  - Xiaoyan Dai
    AU  - Yun Pang
    AU  - Feng Huo
    AU  - Wenlong Li
    AU  - Runlin Han
    Y1  - 2015/12/04
    PY  - 2015
    N1  - https://doi.org/10.11648/j.ajcem.20150305.33
    DO  - 10.11648/j.ajcem.20150305.33
    T2  - American Journal of Clinical and Experimental Medicine
    JF  - American Journal of Clinical and Experimental Medicine
    JO  - American Journal of Clinical and Experimental Medicine
    SP  - 327
    EP  - 331
    PB  - Science Publishing Group
    SN  - 2330-8133
    UR  - https://doi.org/10.11648/j.ajcem.20150305.33
    AB  - The biological function of lipoprotein(a) [Lp(a)] remains elusive although it was identified in 1963. We previously hypothesized that Lp(a) might inhibit pathogens from hijacking host plasminogen (Plg) since apolipoprotein(a) [Apo(a)], a unique protein in Lp(a), shares a high homology with Plg. We demonstrate that Lp(a) bound to recombinant Streptococcal α-enolase (rSEN), which is a surface Plg receptor on group A Streptococcus (GAS). However, recombinant C-terminal lysines-deleted variant of enolase (rSENΔ434-435) did not bind to Lp(a). Moreover, epsilon-aminocaproic acid (EACA), a lysine analog, significantly inhibited the binding of rSEN to Lp(a). Collectively, Lp(a) via its LBS bound to the C-terminal lysines of rSEN. In addition, Lp(a) only competitively blocked the Plg-rSEN interaction but not Plg-rSENΔ434-435 interaction since Plg could also bind to the internal lysine residue of α-enolase. The preliminary study indicated that Lp(a) also interacted with GAS, consequently competitively inhibiting the Plg-GAS binding to some extent. Therefore, Lp(a) might play a limited role in preventing GAS infection since it only partially inhibited the pathogen from recruiting host Plg.
    VL  - 3
    IS  - 5
    ER  - 

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Author Information
  • Research Center of Plasma Lipoprotein Immunology, Inner Mongolia Agricultural University, Huhhot, China

  • Research Center of Plasma Lipoprotein Immunology, Inner Mongolia Agricultural University, Huhhot, China

  • Research Center of Plasma Lipoprotein Immunology, Inner Mongolia Agricultural University, Huhhot, China

  • Research Center of Plasma Lipoprotein Immunology, Inner Mongolia Agricultural University, Huhhot, China

  • Research Center of Plasma Lipoprotein Immunology, Inner Mongolia Agricultural University, Huhhot, China

  • College of Life Science, Inner Mongolia Agricultural University, Huhhot, China

  • Research Center of Plasma Lipoprotein Immunology, Inner Mongolia Agricultural University, Huhhot, China

  • Research Center of Plasma Lipoprotein Immunology, Inner Mongolia Agricultural University, Huhhot, China

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