생명과학회지 (Journal of Life Science)

  • 제17권12호
  • /
  • Pages.1760-1765
  • /
  • 2007
  • /
  • 1225-9918(pISSN)
  • /
  • 2287-3406(eISSN)
한국생명과학회 (Korean Society of Life Science)
권호 표지
DOI QR코드

DOI QR Code

Hsp70 분자 샤페론과 조절인자

Family of Hsp70 Molecular Chaperones and Their Regulators

  • 발행 : 2007.12.30
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

생명체 내에서 일어나는 거의 모든 반응은 단백질이 촉진하거나 수행한다. 단백질은 세포질과 소포체에서 합성될 때 엄격하게 조절된다. 그러나, 새로이 합성된 모든 단백질이 살아남아서 생명을 유지시키는 기능에 관여하게 되지는 않는다. 가장 알맞은 생리학적 in vitro 실험 조건에서 새로이 합성된 단백질의 약 3분의 1 정도는 합성되자마자 proteasome에 의해 빠르게 분해된다고 보고되었다. 또한, 단백질은 합성이 성공적으로 이루어진 이후에는 3차원 구조를 갖기 위해 접힘(folding)이 이루어져야 하고, subunit들은 assembly 과정을 거쳐야 비로소 성숙된 단백질로서 기능을 하게 된다. 어떤 단백질군은 자연적으로 접힘이 일어나는 반면 어떤 단백질군은 분자 샤페론(molecular chaperones)과 folding enzymes의 도움을 받아야만 접힘이 일어난다. 분자 샤페론은 세포 전역에 분포하고 있으며, 세균에서부터 고등 동식물에 이르기까지 모든 생명체에 존재한다. 이들 중 Hsp70군은 많이 연구된 분자 샤페론으로서 지난 10여년 동안 조절인자들이 새로이 발견되어 작용 mechanism이 보다 자세히 밝혀졌다. 본 총설에서 Hsp70군과 그 조절인자들에 대한 전반적인 서술을 하였으며, 이들의 기능이 분자 샤페론 기능 외에 생체 내에서 중요한 기능들이 새롭게 밝혀지고 있어 이들의 작용 mechanism을 조명함으로 이해를 돕고자 한다.

Proteins are involved in promoting or controlling virtually every event on which our lives depend. Proteins are synthesized in cytosol and in the endoplasmic reticulum where their synthesis machinery are tightly controlled. However, not all of newly synthesized proteins are survived and conduct their essential functions to maintain cell's lives. It was reported that one-third of synthesized proteins are rapidly destroyed by proteasome under the most physiological conditions. full-length translated proteins, which survived, must undergo proper folding and assemble process. Some proteins are spontaneously folded while others require molecular chaperones and folding enzymes to be properly folded. Molecular chaperones are ubiquitously present within the subcellular organelles and from bacteria to animals and plants. Among those members of Hsp70 family have been extensively studied and their regulators have been discovered in the last decade. Here, a brief overview is presented for functional mechanism of Hsp70 homologues and the roles of their regulators. Since biological function of Hsp70 family other than chaperonic function are expending the review would give basic understanding of partnership between Hsp70 family and their regulators.

키워드

참고문헌

  1. Albert, B., A. Johnson, J. Lewis, M. Raff, K. Roberts, and P. Walter. 2002. Molecular Biology of The Cell. pp. 355-365, 4th ed., Garland Science. New York
  2. Anttonen, A. K., I. Mahjneh, R. H. Hamalainen, C. Lagier-Tourenne, O. Kopra, L. Waris, M. Anttonen, T. Joensuu, H. Kalimo, A. Paetau, L. Tranebjaerg, D. Chaigne, M. Koenig, O. Eeg-Olofsson, B. Udd, M. Somer, H. Somer and A. E. Lehesjoki. 2005. The gene disrupted in Marinesco-Sjogren syndrome encodes SIL1, an HSPA5 cochaperone. Nat. Genet. 37, 1309-1311 https://doi.org/10.1038/ng1677
  3. Bergman, L. W. and W. M. Kuehl. 1979. Formation of intermolecular disulfide bonds on nascent immunoglobulin polypeptides. J. Biol. Chem. 254, 5690-5694
  4. Bimston, D., J. Song, D. Winchester, S. Takayama, J. C. Reed and R. I. Morimoto. 1998. BAG-1, a negative regulator of Hsp70 chaperone activity, uncouples nucleotide hydrolysis from substrate release. EMBO J. 17, 6871-6878 https://doi.org/10.1093/emboj/17.23.6871
  5. Boisrame, A., J. M. Beckerich and C. Gaillardin. 1996. Sls1p, an endoplasmic reticulum component, is involved in the protein translocation process in the yeast Yarrowia lipolytica. J. Biol. Chem. 271, 11668-11675 https://doi.org/10.1074/jbc.271.20.11668
  6. Boorstein, W. R., T. Ziegelhoffer and E. A. Craig. 1994. Molecular evolution of the HSP70 multigene family. J. Mol. Evol. 38, 1-17
  7. Brehmer, D., S. Rudiger, C. S. Gassler, D. Klostermeier, L. Packschies, J. Reinstein, M. P. Mayer and B. Bukau. 2001. Tuning of chaperone activity of Hsp70 proteins by modulation of nucleotide exchange. Nat. Struct. Biol. 8, 427-432 https://doi.org/10.1038/87588
  8. Chung, K. T., Y. Shen, and L. M. Hendershot. 2002. BAP, a mammalian BiP-associated protein, is a nucleotide exchange factor that regulates the ATPase activity of BiP. J. Biol. Chem. 277, 47557-475663 https://doi.org/10.1074/jbc.M208377200
  9. Crowley, K. S., S. Liao, V. E. Worrell, G. D. Reinhart and A. E. Johnson. 1994. Secretory proteins move through the endoplasmic reticulum membrane via an aqueous, gated pore. Cell 78, 461-471 https://doi.org/10.1016/0092-8674(94)90424-3
  10. Gaut, J. R. and L. M. Hendershot. 1993. Mutations within the nucleotide binding site of immunoglobulin-binding protein inhibit ATPase activity and interfere with release of immunoglobulin heavy chain. J. Biol. Chem. 268, 7248-7255
  11. Haas, I. G. and M. Wabl. 1983. Immunoglobulin heavy chain binding protein. Nature 306, 387-389 https://doi.org/10.1038/306387a0
  12. Hohfeld, J. and S. Jentsch. 1997. GrpE-like regulation of the hsc70 chaperone by the anti-apoptotic protein BAG-1. EMBO J. 16, 6209-6216 https://doi.org/10.1093/emboj/16.20.6209
  13. Johnson, A. E. and M. A. van Waes. 1999. The translocon: a dynamic gateway at the ER membrane. Annu. Rev. Cell Dev. Biol. 15, 799-842 https://doi.org/10.1146/annurev.cellbio.15.1.799
  14. Kabani, M., J. M. Beckerich and C. Gaillardin. 2000. Sls1p stimulates Sec63p-mediated activation of Kar2p in a conformation- dependent manner in the yeast endoplasmic reticulum. Mol. Cell Biol. 20, 6923-6934 https://doi.org/10.1128/MCB.20.18.6923-6934.2000
  15. Kabani, M., J. M. Beckerich and J. L. Brodsky. 2002a. Nucleotide exchange factor for the yeast Hsp70 molecular chaperone Ssa1p. Mol. Cell Biol. 22, 4677-4689 https://doi.org/10.1128/MCB.22.13.4677-4689.2002
  16. Kabani, M., C. McLellan, D. A. Raynes, V. Guerriero and J. L. Brodsky. 2002b. HspBP1, a homologue of the yeast Fes1 and Sls1 proteins, is an Hsc70 nucleotide exchange factor. FEBS Lett. 531, 3339-3342
  17. Kelly, W. L. 1998. The J-domain family and recruitment of chaperone power. Trends Biochem. Sci. 23, 222-227 https://doi.org/10.1016/S0968-0004(98)01215-8
  18. Kowarik, M., S. Küng, B. Martoglio and A. Helenius. 2002. Protein folding during cotranslational translocation in the endoplasmic reticulum. Mol. Cell 10, 769-778 https://doi.org/10.1016/S1097-2765(02)00685-8
  19. Liberek, K., J. Marszalek, D. Ang, C. Georgopoulos and M. Zylicz. 1991. Escherichia coli DnaJ and GrpE heat shock proteins jointly stimulate ATPase activity of DnaK. Proc. Natl. Acad. Sci. USA 88, 2874-2878
  20. Mayer, M. P. and B. Bukau. 2005. Regulation of Hsp70 Chaperones by Co-chaperones. pp. 516, In J Buchner and Y. Kiefhaber (ed), Protein Folding Handbook. Part II, Wiley-VCH
  21. Minami, Y., J. Hohfeld, K. Ohtsuka and F. U. Hartl. 1996. Regulation of the heat-shock protein 70 reaction cycle by the mammalian DnaJ homolog, Hsp40. J. Biol. Chem. 271, 19617-19624 https://doi.org/10.1074/jbc.271.32.19617
  22. Neidhardt, F. C. 1987. Chemical composition of Escherichia coli. In Escherichia coli and Salmonella typhimurium; cellular and molecular biology. pp. 1334-1345, vol 2. Neidhardt, F.C.(ed). ASM., Washington D.C
  23. Netzer, W. J. and F. Ulrich Hartl. 1998. Protein folding in the cytosol: chaperonin-dependent and -independent mechanisms. Trends in Biochem. Sci. 23, 68-73 https://doi.org/10.1016/S0968-0004(97)01171-7
  24. Raynes, D.A and V. Jr. Guerriero. 1998. Inhibition of Hsp70 ATPase activity and protein renaturation by a novel Hsp70-binding protein. J. Biol. Chem. 273, 32883-32888 https://doi.org/10.1074/jbc.273.49.32883
  25. Senderek, J., M. Krieger, C. Stendel, C. Bergmann, M. Moser, N. Breitbach-Faller, S. Rudnik-Schoneborn, A. Blaschek, N.I. Wolf, I. Harting, K. North, J. Smith, F. Muntoni, M. Brockington, S. Quijano-Roy, F. Renault, R. Herrmann, L. M. Hendershot, J. M. Schroder, H. Lochmuller, H. Topaloglu, T. Voit, J. Weis, F. Ebinger and K. Zerres. 2005. Mutations in SIL1 cause Marinesco- Sjogren syndrome, a cerebellar ataxia with cataract and myopathy. Nat. Genet. 37, 1312-1314 https://doi.org/10.1038/ng1678
  26. Sondermann, H., C. Scheufler, C. Schneider, J. Hohfeld, F. U. Hartl and I. Moarefi. 2001. Structure of a Bag/Hsc70 complex: convergent functional evolution of Hsp70 nucleotide exchange factors. Science 291, 1553-1557 https://doi.org/10.1126/science.1057268
  27. Szabo, A., T. Langer, H. Schroder, J. Flanagan, B. Bukau and F. U. Hartl. 1994. The ATP hydrolysis-dependent reaction cycle of the Escherichia coli Hsp70 system DnaK, DnaJ, and GrpE. Proc. Natl. Acad. Sci. USA 91, 10345-10349
  28. Takayama, S., T. Sato, S. Krajewski, K. Kochel, S. Irie, J. A. Millan and J. C. Reed. 1995. Cloning and functional analysis of BAG-1, a novel Bcl-2-binding protein with anti- cell death activity. Cell 80, 279-284 https://doi.org/10.1016/0092-8674(95)90410-7
  29. Takayama, S., D. N. Bimston, S. Matsuzawa, B. C. Freeman, C. Aime-Sempe, Z. Xie, R. I. Morimoto and J. C. Reed. 1997. BAG-1 modulates the chaperone activity of Hsp70/Hsc70. EMBO J. 16, 4887-4896 https://doi.org/10.1093/emboj/16.16.4887
  30. Travers, K. J., C. K. Patil, L. Wodicka, D. J. Lockhart, J. S. Weissman and P. Walter. 2000. Functional and genomic analyses reveal an essential coordination between the unfolded protein response and ER-associated degradation. Cell 101, 249-258 https://doi.org/10.1016/S0092-8674(00)80835-1
  31. Tyson, J. R. and C. J. Stirling. 2000. LHS1 and SIL1 provide a lumenal function that is essential for protein translocation into the endoplasmic reticulum. EMBO J. 19, 6440-6452 https://doi.org/10.1093/emboj/19.23.6440
  32. Wei, J. and L. M. Hendershot. 1995. Characterization of the nucleotide binding properties and ATPase activity of recombinant hamster BiP purified from bacteria. J. Biol. Chem. 270, 26670-26676 https://doi.org/10.1074/jbc.270.44.26670
  33. Wei, J., J. R. Gaut and L. M. Hendershot. 1995. In vitro dissociation of BiP-peptide complexes requires a conformational change in BiP after ATP binding but does not require ATP hydrolysis. J. Biol. Chem. 270, 26677-26682 https://doi.org/10.1074/jbc.270.44.26677
  34. Zeiner, M. and U. Gehring. 1995. A protein that interacts with members of the nuclear hormone receptor family, identification and cDNA cloning. Proc. Natl. Acad. Sci. USA. 92, 11465-11469
  35. Zeiner, M., M. Gebauer and U. Gehring. 1997. Mammalian protein RAP46: an interaction partner and modulator of 70 kDa heat shock proteins. EMBO J. 16, 5483-5490 https://doi.org/10.1093/emboj/16.18.5483
  36. Zhao, L., C. Longo-Guess, B. S. Harris, J. W. Lee and S. L. Ackerman. 2005. Protein accumulation and neurodegeneration in the woozy mutant mouse is caused by disruption of SIL1, a cochaperone of BiP. Nat. Genet. 37, 974-979 https://doi.org/10.1038/ng1620