リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

大学・研究所にある論文を検索できる 「Observing the nonvectorial yet cotranslational folding of a multidomain protein, LDL receptor, in the ER of mammalian cells.」の論文概要。リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。
リケラボ

コピーが完了しました

URLをコピーしました

論文の公開元へ論文の公開元へ
書き出し

Observing the nonvectorial yet cotranslational folding of a multidomain protein, LDL receptor, in the ER of mammalian cells.

Hiroshi Kadokura Yui Dazai Yo Fukuda Naoya Hirai Orie Nakamura Kenji Inaba 東北大学 DOI:10.1073/pnas.2004606117

2020.07.14

概要

Proteins have evolved by incorporating several structural units within a single polypeptide. As a result, multidomain proteins constitute a large fraction of all proteomes. Their domains often fold to their native structures individually and vectorially as each domain emerges from the ribosome or the protein translocation channel, leading to the decreased risk of interdomain misfolding. However, some multidomain proteins fold in the endoplasmic reticulum (ER) nonvectorially via intermediates with nonnative disulfide bonds, which were believed to be shuffled to native ones slowly after synthesis. Yet, the mechanism by which they fold nonvectorially remains unclear. Using two-dimensional (2D) gel electrophoresis and a conformation-specific antibody that recognizes a correctly folded domain, we show here that shuffling of nonnative disulfide bonds to native ones in the most N-terminal region of LDL receptor (LDLR) started at a specific timing during synthesis. Deletion analysis identified a region on LDLR that assisted with disulfide shuffling in the upstream domain, thereby promoting its cotranslational folding. Thus, a plasma membranebound multidomain protein has evolved a sequence that promotes the nonvectorial folding of its upstream domains. These findings demonstrate that nonvectorial folding of a multidomain protein in the ER of mammalian cells is more coordinated and elaborated than previously thought. Thus, our findings alter our current view of how a multidomain protein folds nonvectorially in the ER of living cells.

論文の公開元へ

この論文で使われている画像

関連論文

関連論文をもっと見る

参考文献

1. J. H. Han, S. Batey, A. A. Nickson, S. A. Teichmann, J. Clarke, The folding and evolution of multidomain proteins. Nat. Rev. Mol. Cell Biol. 8, 319–330 (2007).

2. K. C. Stein, J. Frydman, The stop-and-go traffic regulating protein biogenesis: How translation kinetics controls proteostasis. J. Biol. Chem. 294, 2076–2084 (2019).

3. T. Tanaka, N. Hori, S. Takada, How co-translational folding of multi-domain protein is affected by elongation schedule: Molecular simulations. PLOS Comput. Biol. 11, e1004356 (2015).

4. H. K. Choi et al., Watching helical membrane proteins fold reveals a common N-to-C-terminal folding pathway. Science 366, 1150–1156 (2019).

5. W. M. Jacobs, E. I. Shakhnovich, Evidence of evolutionary selection for cotranslational folding. Proc. Natl. Acad. Sci. U.S.A. 114, 11434–11439 (2017).

6. K. Liu, X. Chen, C. M. Kaiser, Energetic dependencies dictate folding mechanism in a complex protein. Proc. Natl. Acad. Sci. U.S.A. 116, 25641–25648 (2019).

7. M. B. Borgia et al., Single-molecule fluorescence reveals sequence-specific misfolding in multidomain proteins. Nature 474, 662–665 (2011).

8. A. Lafita, P. Tian, R. B. Best, A. Bateman, Tandem domain swapping: Determinants of multidomain protein misfolding. Curr. Opin. Struct. Biol. 58, 97–104 (2019).

9. K. C. Stein, A. Kriel, J. Frydman, Nascent polypeptide domain topology and elongation rate direct the cotranslational hierarchy of Hsp70 and TRiC/CCT. Mol. Cell 75, 1117–1130.e5 (2019).

10. C. F. Wright, S. A. Teichmann, J. Clarke, C. M. Dobson, The importance of sequence diversity in the aggregation and evolution of proteins. Nature 438, 878–881 (2005).

11. R. Daniels, B. Kurowski, A. E. Johnson, D. N. Hebert, N-linked glycans direct the cotranslational folding pathway of influenza hemagglutinin. Mol. Cell 11, 79–90 (2003).

12. M. Okumura, H. Kadokura, K. Inaba, Structures and functions of protein disulfide isomerase family members involved in proteostasis in the endoplasmic reticulum. Free Radic. Biol. Med. 83, 314–322 (2015).

13. L. Ellgaard, N. McCaul, A. Chatsisvili, I. Braakman, Co- and post-translational protein folding in the ER. Traffic 17, 615–638 (2016).

14. M. J. Feige, I. Braakman, L. Hendershot, “Disulfide bonds in protein folding and stability” in Oxidative Folding of Proteins: Basic Principles, Cellular Regulation and Engineering, M. J. Feige, Ed. (Royal Society of Chemistry, 2018), pp. 1–33.

15. T. Anelli, R. Sitia, “Mechanisms of oxidative protein folding and thiol-dependent quality control: Tales of cysteines and cystines” in Oxidative Folding of Proteins: Basic Principles, Cellular Regulation and Engineering, M. J. Feige, Ed. (Royal Society of Chemistry, 2018), pp. 249–266.

16. I. Braakman, N. J. Bulleid, Protein folding and modification in the mammalian endoplasmic reticulum. Annu. Rev. Biochem. 80, 71–99 (2011).

17. L. W. Bergman, W. M. Kuehl, Formation of an intrachain disulfide bond on nascent immunoglobulin light chains. J. Biol. Chem. 254, 8869–8876 (1979).

18. W. Chen, J. Helenius, I. Braakman, A. Helenius, Cotranslational folding and calnexin binding during glycoprotein synthesis. Proc. Natl. Acad. Sci. U.S.A. 92, 6229–6233 (1995).

19. A. Jansens, E. van Duijn, I. Braakman, Coordinated nonvectorial folding in a newly synthesized multidomain protein. Science 298, 2401–2403 (2002).

20. F. Pena, A. Jansens, G. van Zadelhoff, I. Braakman, Calcium as a crucial cofactor for low density lipoprotein receptor folding in the endoplasmic reticulum. J. Biol. Chem. 285, 8656–8664 (2010).

21. A. Land, D. Zonneveld, I. Braakman, Folding of HIV-1 envelope glycoprotein involves extensive isomerization of disulfide bonds and conformation-dependent leader peptide cleavage. FASEB J. 17, 1058–1067 (2003).

22. G. J. Poet et al., Cytosolic thioredoxin reductase 1 is required for correct disulfide formation in the ER. EMBO J. 36, 693–702 (2017).

23. B. S. Roberts, M. A. Babilonia-Rosa, L. J. Broadwell, M. J. Wu, S. B. Neher, Lipase maturation factor 1 affects redox homeostasis in the endoplasmic reticulum. EMBO J. 37, 1–17 (2018).

24. T. C. Südhof, J. L. Goldstein, M. S. Brown, D. W. Russell, The LDL receptor gene: A mosaic of exons shared with different proteins. Science 228, 815–822 (1985).

25. J. Gent, I. Braakman, Low-density lipoprotein receptor structure and folding. Cell. Mol. Life Sci. 61, 2461–2470 (2004).

26. H. Jeon, S. C. Blacklow, Structure and physiologic function of the low-density lipoprotein receptor. Annu. Rev. Biochem. 74, 535–562 (2005).

27. O. B. V. Oka, M. A. Pringle, I. M. Schopp, I. Braakman, N. J. Bulleid, ERdj5 is the ER reductase that catalyzes the removal of non-native disulfides and correct folding of the LDL receptor. Mol. Cell 50, 793–804 (2013).

28. M. Koritzinsky et al., Two phases of disulfide bond formation have differing requirements for oxygen. J. Cell Biol. 203, 615–627 (2013).

29. H. Kadokura, J. Beckwith, Detecting folding intermediates of a protein as it passes through the bacterial translocation channel. Cell 138, 1164–1173 (2009).

30. K. Yanagitani, Y. Kimata, H. Kadokura, K. Kohno, Translational pausing ensures membrane targeting and cytoplasmic splicing of XBP1u mRNA. Science 331, 586–589 (2011).

31. T. Fujimoto, K. Inaba, H. Kadokura, Methods to identify the substrates of thioldisulfide oxidoreductases. Protein Sci. 28, 30–40 (2019).

32. M. Molinari, A. Helenius, Glycoproteins form mixed disulphides with oxidoreductases during folding in living cells. Nature 402, 90–93 (1999).

33. M. Molinari, A. Helenius, Analyzing cotranslational protein folding and disulfide formation by diagonal sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Methods Enzymol. 348, 35–42 (2002).

34. N. B. Pedersen et al., Low density lipoprotein receptor class A repeats are O-glycosylated in linker regions. J. Biol. Chem. 289, 17312–17324 (2014).

35. K. Braunger et al., Structural basis for coupling protein transport and N-glycosylation at the mammalian endoplasmic reticulum. Science 360, 215–219 (2018).

36. A. T. Nguyen, T. Hirama, V. Chauhan, R. Mackenzie, R. Milne, Binding characteristics of a panel of monoclonal antibodies against the ligand binding domain of the human LDLr. J. Lipid Res. 47, 1399–1405 (2006).

37. N. Cherepanova, S. Shrimal, R. Gilmore, N-linked glycosylation and homeostasis of the endoplasmic reticulum. Curr. Opin. Cell Biol. 41, 57–65 (2016).

38. O. Szekely et al., Identification and rationalization of kinetic folding intermediates for a low-density lipoprotein receptor ligand-binding module. Biochemistry 57, 4776–4787 (2018).

39. Y. Sato et al., Synergistic cooperation of PDI family members in peroxiredoxin 4-driven oxidative protein folding. Sci. Rep. 3, 2456 (2013).

40. L. W. Bergman, W. M. Kuehl, Formation of intermolecular disulfide bonds on nascent immunoglobulin polypeptides. J. Biol. Chem. 254, 5690–5694 (1979).

41. S.-S. Chng et al., Disulfide rearrangement triggered by translocon assembly controls lipopolysaccharide export. Science 337, 1665–1668 (2012).

42. M. J. Feige, J. Behnke, T. Mittag, L. M. Hendershot, Dimerization-dependent folding underlies assembly control of the clonotypic αβT cell receptor chains. J. Biol. Chem. 290, 26821–26831 (2015).

43. T. Fujimoto et al., Identification of the physiological substrates of PDIp, a pancreasspecific protein-disulfide isomerase family member. J. Biol. Chem. 293, 18421–18433 (2018).

参考文献をもっと見る

全国の大学の
卒論・修論・学位論文
を
一発検索！

この論文の関連論文を見る