Signal Peptide-Binding Drug as a Selective Inhibitor of Co-Translational Protein Translocation

PLoS Biology

Volumn 12, Issue 12, 2014, Pages

  Vermeire, Kurt ^a,b,c   Bell, Thomas W ^d   Van Puyenbroeck, Victor ^a   Giraut, Anne ^a   Noppen, Sam ^a   Liekens, Sandra ^a   Schols, Dominique ^a   Hartmann, Enno ^b   Kalies, Kai Uwe ^b   Marsh, Mark ^c  

^a REGA INSTITUTE FOR MEDICAL RESEARCH   (Belgium)

^b UNIVERSITY OF LÜBECK   (Germany)

^c UNIVERSITY COLLEGE LONDON   (United Kingdom)

^d UNIVERSITY OF NEVADA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CD4 ANTIGEN; CYCLOTRIAZADISULFONAMIDE; PROTEIN INHIBITOR; SIGNAL PEPTIDE; UNCLASSIFIED DRUG; PROTEIN SYNTHESIS INHIBITOR; SULFONAMIDE;

AMINO TERMINAL SEQUENCE; ARTICLE; CONCENTRATION RESPONSE; CONTROLLED STUDY; CYTOSOL; DOWN REGULATION; DRUG PROTEIN BINDING; DRUG SELECTIVITY; DRUG STRUCTURE; DRUG TARGETING; ENDOPLASMIC RETICULUM; FLOW CYTOMETRY; HUMAN; HUMAN CELL; HYDROPHOBICITY; IN VITRO STUDY; INHIBITION KINETICS; PROTEIN CLEAVAGE; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN FOLDING; PROTEIN LOCALIZATION; PROTEIN TARGETING; SIGNAL TRANSDUCTION; SURFACE PLASMON RESONANCE; AMINO ACID SEQUENCE; CHEMICAL PHENOMENA; CHEMISTRY; DRUG EFFECTS; METABOLISM; MOLECULAR GENETICS; PROTEIN CONFORMATION; PROTEIN SYNTHESIS; PROTEIN TRANSPORT;

EUKARYOTA;

AMINO ACID SEQUENCE; ANTIGENS, CD4; DOWN-REGULATION; HUMANS; HYDROPHOBIC AND HYDROPHILIC INTERACTIONS; MOLECULAR SEQUENCE DATA; PROTEIN BIOSYNTHESIS; PROTEIN CONFORMATION; PROTEIN SORTING SIGNALS; PROTEIN SYNTHESIS INHIBITORS; PROTEIN TRANSPORT; SULFONAMIDES;

EID: 84924086061     PISSN: 15449173     EISSN: 15457885     Source Type: Journal    
DOI: 10.1371/journal.pbio.1002011     Document Type: Article

References (63)

1. Littman DR, (1987) The structure of the CD4 and CD8 genes. Annu Rev Immunol 5: 561–584.
2. Dalgleish AG, Beverley PC, Clapham PR, Crawford DH, Greaves MF, et al. (1984) The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature 312: 763–767.
3. Klatzmann D, Champagne E, Chamaret S, Gruest J, Guetard D, et al. (1984) T-lymphocyte T4 molecule behaves as the receptor for human retrovirus LAV. Nature 312: 767–768.
4. Conti L, Varano B, Gauzzi MC, Matarrese P, Federico M, et al. (2000) Impairment of human immunodeficiency virus type 1 (HIV-1) entry into Jurkat T cells by constitutive expression of the HIV-1 vpr protein: role of CD4 down-modulation. J Virol 74: 10207–10211.
5. Nokta MA, Li XD, Nichols J, Mallen M, Pou A, et al. (2001) Chemokine/CD4 receptor density ratios correlate with HIV replication in lymph node and peripheral blood of HIV-infected individuals. AIDS 15: 161–169.
6. Xiang J, McLinden JH, Rydze RA, Chang Q, Kaufman TM, et al. (2009) Viruses within the Flaviviridae decrease CD4 expression and inhibit HIV replication in human CD4+ cells. J Immunol 183: 7860–7869.
7. Lisco A, Grivel JC, Biancotto A, Vanpouille C, Origgi F, et al. (2007) Viral interactions in human lymphoid tissue: Human herpesvirus 7 suppresses the replication of CCR5-tropic human immunodeficiency virus type 1 via CD4 modulation. J Virol 81: 708–717.
8. Vermeire K, Bell TW, Choi HJ, Jin Q, Samala MF, et al. (2003) The Anti-HIV potency of cyclotriazadisulfonamide analogs is directly correlated with their ability to down-modulate the CD4 receptor. Mol Pharmacol 63: 203–210.
9. Beaumier CM, Harris LD, Goldstein S, Klatt NR, Whitted S, et al. (2009) CD4 downregulation by memory CD4+ T cells in vivo renders African green monkeys resistant to progressive SIVagm infection. Nat Med 15: 879–885.
10. Geleziunas R, Bour S, Wainberg MA, (1994) Cell surface down-modulation of CD4 after infection by HIV-1. FASEB J 8: 593–600.
11. Pelchen-Matthews A, Parsons IJ, Marsh M, (1993) Phorbol ester-induced downregulation of CD4 is a multistep process involving dissociation from p56lck, increased association with clathrin-coated pits, and altered endosomal sorting. J Exp Med 178: 1209–1222.
12. Willey RL, Maldarelli F, Martin MA, Strebel K, (1992) Human immunodeficiency virus type 1 Vpu protein induces rapid degradation of CD4. J Virol 66: 7193–7200.
13. Margottin F, Bour SP, Durand H, Selig L, Benichou S, et al. (1998) A novel human WD protein, h-beta TrCp, that interacts with HIV-1 Vpu connects CD4 to the ER degradation pathway through an F-box motif. Mol Cell 1: 565–574.
14. Garcia JV, Miller AD, (1991) Serine phosphorylation-independent downregulation of cell-surface CD4 by nef. Nature 350: 508–511.
15. Jin YJ, Zhang X, Boursiquot JG, Burakoff SJ, (2004) CD4 phosphorylation partially reverses Nef down-regulation of CD4. J Immunol 173: 5495–5500.
16. Park E, Rapoport TA, (2012) Mechanisms of Sec61/SecY-mediated protein translocation across membranes. Annu Rev Biophys 41: 21–40.
17. Hegde RS, Keenan RJ, (2011) Tail-anchored membrane protein insertion into the endoplasmic reticulum. Nat Rev Mol Cell Biol 12: 787–798.
18. Vermeire K, Zhang Y, Princen K, Hatse S, Samala MF, et al. (2002) CADA inhibits human immunodeficiency virus and human herpesvirus 7 replication by down-modulation of the cellular CD4 receptor. Virology 302: 342–353.
19. Vermeire K, Princen K, Hatse S, De Clercq E, Dey K, et al. (2004) CADA, a novel CD4-targeted HIV inhibitor, is synergistic with various anti-HIV drugs in vitro. AIDS 18: 2115–2125.
20. Rudd CE, Trevillyan JM, Dasgupta JD, Wong LL, Schlossman SF, (1988) The CD4 receptor is complexed in detergent lysates to a protein-tyrosine kinase (pp58) from human T lymphocytes. Proc Natl Acad Sci U S A 85: 5190–5194.
21. Blobel G, Dobberstein B, (1975) Transfer of proteins across membranes. I. Presence of proteolytically processed and unprocessed nascent immunoglobulin light chains on membrane-bound ribosomes of murine myeloma. J Cell Biol 67: 835–851.
22. Wickner WT, Lodish HF, (1985) Multiple mechanisms of protein insertion into and across membranes. Science 230: 400–407.
23. von Heijne G, (1985) Signal sequences. The limits of variation. J Mol Biol 184: 99–105.
24. Jungnickel B, Rapoport TA, (1995) A posttargeting signal sequence recognition event in the endoplasmic reticulum membrane. Cell 82: 261–270.
25. Kalies KU, Stokes V, Hartmann E, (2008) A single Sec61-complex functions as a protein-conducting channel. Biochim Biophys Acta 1783: 2375–2383.
26. Rapoport TA, (2007) Protein translocation across the eukaryotic endoplasmic reticulum and bacterial plasma membranes. Nature 450: 663–669.
27. Shaw AS, Rottier PJ, Rose JK, (1988) Evidence for the loop model of signal-sequence insertion into the endoplasmic reticulum. Proc Natl Acad Sci U S A 85: 7592–7596.
28. Rutkowski DT, Lingappa VR, Hegde RS, (2001) Substrate-specific regulation of the ribosome- translocon junction by N-terminal signal sequences. Proc Natl Acad Sci U S A 98: 7823–7828.
29. Goder V, Spiess M, (2003) Molecular mechanism of signal sequence orientation in the endoplasmic reticulum. EMBO J 22: 3645–3653.
30. Rösch K, Naeher D, Laird V, Goder V, Spiess M, (2000) The topogenic contribution of uncharged amino acids on signal sequence orientation in the endoplasmic reticulum. J Biol Chem 275: 14916–14922.
31. Eusebio A, Friedberg T, Spiess M, (1998) The role of the hydrophobic domain in orienting natural signal sequences within the ER membrane. Exp Cell Res 241: 181–185.
32. Devaraneni PK, Conti B, Matsumura Y, Yang Z, Johnson AE, et al. (2011) Stepwise insertion and inversion of a type II signal anchor sequence in the ribosome-Sec61 translocon complex. Cell 146: 134–147.
33. Heinrich SU, Mothes W, Brunner J, Rapoport TA, (2000) The Sec61p complex mediates the integration of a membrane protein by allowing lipid partitioning of the transmembrane domain. Cell 102: 233–244.
34. Harant H, Lettner N, Hofer L, Oberhauser B, de Vries JE, et al. (2006) The translocation inhibitor CAM741 interferes with vascular cell adhesion molecule 1 signal peptide insertion at the translocon. J Biol Chem 281: 30492–30502.
35. Plath K, Mothes W, Wilkinson BM, Stirling CJ, Rapoport TA, (1998) Signal sequence recognition in posttranslational protein transport across the yeast ER membrane. Cell 94: 795–807.
36. Kocik L, Junne T, Spiess M, (2012) Orientation of internal signal-anchor sequences at the Sec61 translocon. J Mol Biol 424: 368–378.
37. Reithinger JH, Kim JE, Kim H, (2013) Sec62 protein mediates membrane insertion and orientation of moderately hydrophobic signal anchor proteins in the endoplasmic reticulum (ER). J Biol Chem 288: 18058–18067.
38. von Heijne G, (1986) The distribution of positively charged residues in bacterial inner membrane proteins correlates with the trans-membrane topology. EMBO J 5: 3021–3027.
39. Hartmann E, Rapoport TA, Lodish HF, (1989) Predicting the orientation of eukaryotic membrane-spanning proteins. Proc Natl Acad Sci U S A 86: 5786–5790.
40. Sakaguchi M, Tomiyoshi R, Kuroiwa T, Mihara K, Omura T, (1992) Functions of signal and signal-anchor sequences are determined by the balance between the hydrophobic segment and the N-terminal charge. Proc Natl Acad Sci U S A 89: 16–19.
41. Nilsson IM, von Heijne G, (1993) Determination of the distance between the oligosaccharyltransferase active site and the endoplasmic reticulum membrane. J Biol Chem 268: 5798–5801.
42. Karamyshev AL, Patrick AE, Karamysheva ZN, Griesemer DS, Hudson H, et al. (2014) Inefficient SRP interaction with a nascent chain triggers a mRNA quality control pathway. Cell 156: 146–157.
43. Higy M, Junne T, Spiess M, (2004) Topogenesis of membrane proteins at the endoplasmic reticulum. Biochemistry 43: 12716–12722.
44. Mothes W, Prehn S, Rapoport TA, (1994) Systematic probing of the environment of a translocating secretory protein during translocation through the ER membrane. EMBO J 13: 3973–3982.
45. Hessa T, Meindl-Beinker NM, Bernsel A, Kim H, Sato Y, et al. (2007) Molecular code for transmembrane-helix recognition by the Sec61 translocon. Nature 450: 1026–1030.
46. Conti BJ, Elferich J, Yang Z, Shinde U, Skach WR, (2014) Cotranslational folding inhibits translocation from within the ribosome-Sec61 translocon complex. Nat Struct Mol Biol 21: 228–235.
47. Bell TW, Anugu S, Bailey P, Catalano VJ, Dey K, et al. (2006) Synthesis and structure-activity relationship studies of CD4 down-modulating cyclotriazadisulfonamide (CADA) analogues. J Med Chem 49: 1291–1312.
48. Demillo VG, Goulinet-Mateo F, Kim J, Schols D, Vermeire K, et al. (2011) Unsymmetrical cyclotriazadisulfonamide (CADA) compounds as human CD4 receptor down-modulating agents. J Med Chem 54: 5712–5721.
49. Besemer J, Harant H, Wang S, Oberhauser B, Marquardt K, et al. (2005) Selective inhibition of cotranslational translocation of vascular cell adhesion molecule 1. Nature 436: 290–293.
50. Garrison JL, Kunkel EJ, Hegde RS, Taunton J, (2005) A substrate-specific inhibitor of protein translocation into the endoplasmic reticulum. Nature 436: 285–289.
51. MacKinnon AL, Garrison JL, Hegde RS, Taunton J, (2007) Photo-leucine incorporation reveals the target of a cyclodepsipeptide inhibitor of cotranslational translocation. J Am Chem Soc 129: 14560–14561.
52. MacKinnon AL, Paavilainen VO, Sharma A, Hegde RS, Taunton J, (2014) An allosteric Sec61 inhibitor traps nascent transmembrane helices at the lateral gate. Elife 3: e01483.
53. Maifeld SV, MacKinnon AL, Garrison JL, Sharma A, Kunkel EJ, et al. (2011) Secretory protein profiling reveals TNF-alpha inactivation by selective and promiscuous Sec61 modulators. Chem Biol 18: 1082–1088.
54. Kim J, Choi I, Park JY, Kang SW, (2013) Specific inhibition of hamster prion protein translocation by the dodecadepsipeptide valinomycin. Exp Cell Res 319: 2049–2057.
55. Ryoo IJ, Park HR, Choo SJ, Hwang JH, Park YM, et al. (2006) Selective cytotoxic activity of valinomycin against HT-29 Human colon carcinoma cells via down-regulation of GRP78. Biol Pharm Bull 29: 817–820.
56. Cross BC, McKibbin C, Callan AC, Roboti P, Piacenti M, et al. (2009) Eeyarestatin I inhibits Sec61-mediated protein translocation at the endoplasmic reticulum. J Cell Sci 122: 4393–4400.
57. Hall BS, Hill K, McKenna M, Ogbechi J, High S, et al. (2014) The pathogenic mechanism of the Mycobacterium ulcerans virulence factor, mycolactone, depends on blockade of protein translocation into the ER. PLoS Pathog 10: e1004061.
58. Liu Y, Law BK, Luesch H, (2009) Apratoxin a reversibly inhibits the secretory pathway by preventing cotranslational translocation. Mol Pharmacol 76: 91–104.
59. Benkirane M, Jeang KT, Devaux C, (1994) The cytoplasmic domain of CD4 plays a critical role during the early stages of HIV infection in T-cells. EMBO J 13: 5559–5569.
60. Schweizer A, Rusert P, Berlinger L, Ruprecht CR, Mann A, et al. (2008) CD4-specific designed ankyrin repeat proteins are novel potent HIV entry inhibitors with unique characteristics. PLoS Pathog 4: e1000109.
61. Connolly T, Gilmore R, (1986) Formation of a functional ribosome-membrane junction during translocation requires the participation of a GTP-binding protein. J Cell Biol 103: 2253–2261.
62. Gay W, Lauret E, Boson B, Larghero J, Matheux F, et al. (2004) Low autocrine interferon beta production as a gene therapy approach for AIDS: Infusion of interferon beta-engineered lymphocytes in macaques chronically infected with SIVmac251. Retrovirology 1: 29.
63. Bijlmakers MJ, Marsh M, (1999) Trafficking of an acylated cytosolic protein: newly synthesized p56(lck) travels to the plasma membrane via the exocytic pathway. J Cell Biol 145: 457–468.