International Journal of Advanced Culture Technology

The International Promotion Agency of Culture Technology (국제문화기술진흥원)
권호 표지
DOI QR코드

DOI QR Code

The design for therapeutic agents of Leucine Rich Repeat protein using bioinformatics

  • Kim, Seong Yeol (Department of Senior Healthcare, BK21 Plus Program, Graduate School, Eulji University) ;
  • Park, Beom Seok (Department of Senior Healthcare, BK21 Plus Program, Graduate School, Eulji University)
  • Received : 2019.10.25
  • Accepted : 2019.11.14
  • Published : 2019.12.31
Download PDF
⟨ Previous Next ⟩

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by progressive joint deterioration; Furthermore, RA can also affect body tissues, including the skin, eyes, lungs, heart and blood vessels. The early stages of RA can be difficult to diagnose because the signs and symptoms mimic those of many other diseases. It is not known exactly what triggers the onset of RA and how to cure the disease. But recent discoveries indicate that remission of symptoms is more likely when treatment begins early with strong medications known as disease-modifying anti-rheumatic drugs (DMARDs). Tumor necrosis factor (TNF) inhibitors are typical examples of biotherapies that have been developed for RA. The substances may occur naturally in the body or may be made in the laboratory. Other biological therapies care biological response modifiers (BRMs)such as monoclonal antibodies, interferon, interleukin-2 (IL-2) and a protein binder using repeat units. These substances play significant anti-inflammatory roles. Proteins with recurrent, conserved amino acid stretches mediate interactions among proteins for essential biological functions; for example, ankyrin (ANK), Heat repeat protein (HEAT), armadillo repeat protein (ARM) and tetratricopeptide repeats (TPR). Here, we describe Leucine rich repeats (LRR) that ideally fold together to form a solenoid protein domain and is more applicable to our current study than the previously mentioned examples. Although BRMs have limitations in terms of immunogenicity and effector functions, among other factors, in the context therapeutic use and for proteomics research, We has become clear that repeat-unit-derived binding proteins will increasingly be used in biotechnology and medicine.

Keywords

References

  1. P. Miossec "Introduction: 'Why is there persistent disease despite aggressive therapy of rheumatoid arthritis?'" Arthritis Res Ther. Vol. 16, No. 3 pp. 113, 2014. doi:10.1186/ar4592
  2. E.G. Favalli, M.G. Raimondo, A. Becciolini, C. Crotti, M. Biggioggero, R. Caporali "The management of first-line biologic therapy failures in rheumatoid arthritis: Current practice and future perspectives.", Autoimmun Rev. Vol. 16, No. 12, pp. 1185-1195, 2017. doi: 10.1016/j.autrev
  3. Y. Lee, J.J. Lee, S. Kim, S.C. Lee, J. Han, W. Heu, K. Park, H.J. Kim, H.K. Cheong, D. Kim, H.S. Kim, K.W. Lee "Dissecting the critical factors for thermodynamic stability of modular proteins using molecular modeling approach." PLoS One. Vol. 9, No. 5, pp: e98243, 2014. doi:10.1371/journal.pone.0098243
  4. J.W. Um, K.H. Kim, B.S. Park, Y. Choi, D. Kim, C.Y. Kim, S.J. Kim, M. Kim, J.S. Ko, S.G. Lee, G. Choii, J. Nam, W.D. Heo, E. Kim, J.O. Lee, J. Ko, H.M. Kim "Structural basis for LAR-RPTP/Slitrk complex-mediated synaptic adhesion." Nat Commun. Vol. 14, No. 5, pp: 5423, 2014. doi:10.1038/ncomms6423
  5. M.A. Andrade, C. Perez-Iratxeta, C.P. Ponting "Protein repeats: structures, functions, and evolution." J Struct Biol. Vo1.134, No. 2-3, pp: 117-131, 2001. doi: 10.1006/jsbi.2001.4392
  6. E.R. Main, A.R. Lowe, S.G. Mochrie, S.E. Jackson, L. Regan "A recurring theme in protein engineering: the design, stability and folding of repeat proteins." Curr Opin Struct Biol. Vol. 5, No. 4, pp:464-471, 2005. doi:10.1016/j.sbi.2005.07.003
  7. B. Kobe, A.V. Kajava "When protein folding is simplified to protein coiling: the continuum of solenoid protein structures." Trends Biochem Sci. Vol. 25, No. 10, pp:509-515, 2000. doi:10.1016/s0968-0004(00)01667-4
  8. F. Parmeggiani, R. Pellarin, A.P. Larsen, G. Varadamsetty, M.T. Stumpp, O. Zerbe, A. Caflisch, A. Pluckthun "Designed armadillo repeat proteins as general peptide-binding scaffolds: consensus design and computational optimization of the hydrophobic core." J Mol Biol. Vol. 7, No. 376, pp:1282-1304, 2008. doi: 10.1016/j.jmb.2007.12.014
  9. E.R. Main, S.E. Jackson, L. Regan "The folding and design of repeat proteins: reaching a consensus." Curr Opin Struct Biol. Vol. 18, No. 4, pp:482-489, 2003. doi:10.1016/s0959-440x(03)00105-2
  10. A. Skerra "Alternative non-antibody scaffolds for molecular recognition." Curr Opin Biotechnol. Vol. 18, No. 4, pp:295-304, 2007. doi:10.1016/j.copbio.2007.04.010
  11. B. Kobe, A.V. Kajava "The leucine-rich repeat as a protein recognition motif." Curr Opin Struct Biol. Vol. 11, No. 6, pp:725-732, 2001. doi:10.1016/s0959-440x(01)00266-4
  12. J.Y. Kang, X. Nan, M.S. Jin, S.J. Youn, Y.H. Ryu, S. Mah, S.H. Han, H. Lee, S.G. Paik, L.O. Lee "Recognition of lipopeptide patterns by Toll-like receptor 2-Toll-like receptor 6 heterodimer." Immunity. Vol. 31, No. 6, pp:873-884, 2009. doi: 10.1016/j.immuni.2009.09.018
  13. B.S. Park, D.H. Song, H.M. Kim, B.S. Choi, H. Lee, J.O. Lee "The structural basis of lipopolysaccharide recognition by the TLR4-MD-2 complex." Nature. Vol. 458, No. 7242, pp:1191-1195, 2009. doi: 10.1038/nature07830
  14. H.M. Kim, B.S. Park, J.I. Kim, S.E. Kim, J. Lee, S.C. Oh, P. Enkhbayar, N. Matsushima, H. Lee, O.J. Yoo, J.O. Lee "Crystal structure of the TLR4-MD-2 complex with bound endotoxin antagonist Eritoran." Cell, Vol. 130, No. 5, pp. 906-917, 2007. doi:10.1016/j.cell.2007.08.002
  15. M.S. Jin, J.O. Lee "Structures of the toll-like receptor family and its ligand complexes." Immunity, Vol. 29, No. 2, pp.182-191, 2008. doi: 10.1016/j.immuni.2008.07.007
  16. M.S. Jin, J.O. Lee "Application of hybrid LRR technique to protein crystallization." BMB Rep, Vol. 41, No. 5, pp:353-357, 2008. doi:10.5483/bmbrep.2008.41.5.353
  17. K. Jung, J.E. Lee, H.Z. Kim, H.M. Kim, B.S. Park, S.I. Hwang, J.O. Lee, S.C. Kim, G.Y. Koh "Tolllike receptor 4 decoy, TOY, attenuates gram-negative bacterial sepsis." PLoS One. Vol. 4, No. 10, pp:e7403, 2009. doi: 10.1371/journal.pone.0007403
  18. S.C. Lee, K. Park, J. Han, J.J. Lee, H.J. Kim, S. Hong, W. Heu, Y.J. Kim, J.S. Ha, S.G. Lee, H.K. Cheong, Y.H. Jeon, D. Kim, H.S. Kim "Design of a binding scaffold based on variable lymphocyte receptors of jawless vertebrates by module engineering." Proc Natl Acad Sci U S A., Vol. 109, No. 9, pp:3299-3304, 2012. doi: 10.1073/pnas.1113193109
  19. J.J. Lee, H.J. Kim, C.S. Yang, H.H. Kyeong, J.M. Choi, D.E. Hwang, J.M. Yuk, K. Park, Y.J. Kim, S.G. Lee, D. Kim, E.K. Jo, H.K. Cheong, H.S. Kim "A high-affinity protein binder that blocks the IL-6/STAT3 signaling pathway effectively suppresses non-small cell lung cancer." Mol Ther. Vol. 22, No. 7, pp:1254-1265, 2014. doi: 10.1038/mt.2014.59
  20. H.K. Binz, A. Kohl, A. Pluckthun, M.G. Grutter "Crystal structure of a consensus-designed ankyrin repeat protein: implications for stability" Proteins, Vol. 65, No. 2, pp:280-284, 2006. doi:10.1002/prot.20930
  21. E.R. Main, Y. Xiong, M.J. Cocco, L. D'Andrea, L. Regan "Design of stable alpha-helical arrays from an idealized TPR motif." Structure, Vol. 11, No. 5, pp:497-508, 2003. doi:10.1016/s0969-2126(03)00076-5
  22. B.W. Han, B.R. Herrin, M.D. Cooper, I.A. Wilson "Antigen recognition by variable lymphocyte receptors." Science, Vol. 321, No. 5897, pp:1834-1837, 2008. doi: 10.1126/science.1162484
  23. H.K. Kim "Effects of Korean Radish on DSS-Induced Ulcerative Colitis in Mice" IJACT, Vol. 6, No. 4, 97-108, 2018. doi https://doi.org/10.17703//IJACT2018.6.4.97
  24. H.K. Kim, J.H. Lee "Anticardiovascular Diseases Effects of Fermented Garlic and Fermented Chitosan" IJACT, Vol. 6, No. 4, 109-115, 2018. doi https://doi.org/10.17703//IJACT2018.6.4.109