The crystal structure of the proprotein processing proteinase furin explains its stringent specificity

Nature Structural Biology

Volumn 10, Issue 7, 2003, Pages 520-526

  Henrich, Stefan ^a   Cameron, Angus ^b,e   Bourenkov, Gleb P ^c   Kiefersauer, Reiner ^a,d   Huber, Robert ^a   Lindberg, Iris ^b   Bode, Wolfram ^a   Than, Manuel E ^a  

^a MAX PLANCK INSTITUTE OF BIOCHEMISTRY   (Germany)

^b LOUISIANA STATE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c MAX PLANCK UNIT FOR STRUCTURAL MOLECULAR BIOLOGY   (Germany)

^d PROTEROS BIOSTRUCTURES GMBH   (Germany)

^e UNIVERSITY OF BRISTOL   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ARGININE; CALCIUM DEPENDENT ENDOPROTEINASE; DECANOYLARGINYLVALYLLYSYLARGININE CHLOROMETHYLKETONE; FURIN; LYSINE; PEPTIDE HORMONE; PROHORMONE PROPROTEIN CONVERTASE; PROTEINASE; UNCLASSIFIED DRUG;

ANTHRAX; ARTICLE; CRYSTAL STRUCTURE; EBOLA VIRUS; EMBRYO DEVELOPMENT; ENZYME ACTIVE SITE; ENZYME SPECIFICITY; EUKARYOTE; HOMEOSTASIS; METASTASIS; NERVE DEGENERATION; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN INTERACTION; PROTEIN MOTIF; PROTEIN PROCESSING; PROTEIN SECRETION; PROTEIN STRUCTURE; VIRUS STRAIN;

AMINO ACID SEQUENCE; ANIMALS; CATALYTIC DOMAIN; CRYSTALLOGRAPHY, X-RAY; ENZYME INHIBITORS; FURIN; MICE; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; PROTEIN CONFORMATION; SEQUENCE HOMOLOGY, AMINO ACID; SUBSTRATE SPECIFICITY; SUBTILISINS;

ANTHRAX; BACTERIA (MICROORGANISMS); EBOLA VIRUS; EUKARYOTA; MAMMALIA;

EID: 0037743535     PISSN: 10728368     EISSN: None     Source Type: Journal    
DOI: 10.1038/nsb941     Document Type: Article

References (36)

1. Nakayama, K. Furin: a mammalian subtilisin/Kex2p-like endoprotease involved in processing of a wide variety of precursor proteins. Biochem. J. 327, 625-635 (1997).
2. Steiner, D.F. The proprotein convertases. Curr. Opin. Chem. Biol. 3, 31-39 (1998).
3. Seidah, N.G. & Chretien, M. Proprotein and prohormone convertases: a family of subtilases generating diverse bioactive polypeptides. Brain Res. 848, 45-62 (1999).
4. Thomas, G. Furin at the cutting edge: from protein traffic to embryogenesis and disease. Nat. Rev. Mol. Cell Biol. 3, 753-766 (2002).
5. Rockwell, N.C., Krysan, D.J., Komiyama, T. & Fuller, R.S. Precursor processing by Kex2/furin proteases. Chem. Rev. 102, 4525-4548 (2002).
6. Fuller, R.S., Brake, A.J. & Thorner, J. Intracellular targeting and structural conservation of a prohormone-processing endoprotease. Science 246, 482-486 (1989).
7. Siezen, R.J. & Leunissen, J.A. Subtilases: the superfamily of subtilisin-like serine proteases. Protein Sci. 6, 501-523 (1997).
8. Anderson, E.D., VanSlyke, J.K., Thulin, C.D., Jean, F. & Thomas, G. Activation of the furin endoprotease is a multiple-step process: requirements for acidification and internal propeptide cleavage. EMBO J. 16, 1508-1518 (1997).
9. Anderson, E.D. et al. The ordered and compartment-specific autoproteolytic removal of the furin intramolecular chaperone is required for enzyme activation. J. Biol. Chem. 277, 12879-12890 (2002).
10. Roebroek, A.J. et al. Failure of ventral closure and axial rotation in embryos lacking the proprotein convertase Furin. Development 125, 4863-4876 (1998).
11. Molloy, S.S., Bresnahan, P.A., Leppla, S.H., Klimpel, KR & Thomas, G. Human furin is a calcium-dependent serine endoprotease that recognizes the sequence Arg-X-X-Arg and efficiently cleaves anthrax toxin protective antigen. J. Biol. Chem. 267, 16396-16402 (1992).
12. Volchkov, V.E., Feldmann, H., Volchkova, V.A. & Klenk, H.D. Processing of the Ebola virus glycoprotein by the proprotein convertase furin. Proc. Natl. Acad. Sci. USA 95, 5762-5767 (1998).
13. Hallenberger, S. et al. Inhibition of furin-mediated cleavage activation of HIV-1 glycoprotein gp160. Nature. 360, 358-361 (1992).
14. Tangrea, M.A., Bryan, P.N., Sari, N. & Orban, J. Solution structure of the prohormone convertase 1 pro-domain from Mus musculus. J. Mol. Biol. 320, 801-812 (2002).
15. Siezen, R.J., Creemers, J.W. & Van de Ven, W.J. Homology modelling of the catalytic domain of human furin. A model for the eukaryotic subtilisin-like proprotein convertases. Eur. J. Biochem. 222, 255-266 (1994).
16. Ueda, K. et al. Mutational analysis of predicted interactions between the catalytic and P domains of prohormone convertase 3 (PC3/PC1). Proc. Natl. Acad. Sci. USA 100, 5622-5627 (2003).
17. Bode, W., Papamokos, E. & Musil, D. The high-resolution X-ray crystal structure of the complex formed between subtilisin Carlsberg and eglin c, an elastase inhibitor from the leech Hirudo medicinalis. Eur. J. Biochem. 166, 673-692 (1987).
18. Lusson, J. et al. The integrity of the RRGDL sequence of the proprotein convertase PC1 is critical for its zymogen and C-terminal processing and for its cellular trafficking. Biochem. J. 326, 737-744 (1997).
19. Zhou, A., Martin, S., Lipkind, G., LaMendola, J. & Steiner, D.F. Regulatory roles of the P domain of the subtilisin-like prohormone convertases. J. Biol. Chem. 273, 11107-11114 (1998).
20. Bhattacharjya, S. et al. pH-induced conformational transitions of a molten-globule-like state of the inhibitory prodomain of furin: implications for zymogen activation. Protein Sci. 10, 934-942 (2001).
21. Gallagher, T., Gilliland, G., Wang, L. & Bryan, P. The prosegment-subtilisin BPN' complex: crystal structure of a specific 'foldase'. Structure 3, 907-914 (1995).
22. Jean, F., Boudreault, A., Basak, A., Seidah, N.G. & Lazure, C. Fluorescent peptidyl substrates as an aid in studying the substrate specificity of human prohormone convertase PC1 and human furin and designing a potent irreversible inhibitor. J. Biol. Chem. 270, 19225-19231 (1995).
23. Fugère, M. et al. Inhibitory potency and specificity of subtilase-like pro-protein convertase (SPC) prodomains. J. Biol. Chem. 277, 7648-7656 (2002).
24. Cameron, A., Appel, J., Houghten, R.A. & Lindberg, I. Polyarginines are potent furin inhibitors. J. Biol. Chem. 275, 36741-36749 (2000).
25. Basak, A., Zhong, M., Munzer, J.S., Chretien, M. & Seidah, N.G. Implication of the proprotein convertases furin, PC5 and PC7 in the cleavage of surface glycoproteins of Hong Kong, Ebola and respiratory syncytial viruses: a comparative analysis with fluorogenic peptides. Biochem. J. 353, 537-545 (2001).
26. Sarac, M.S., Cameron, A. & Lindberg, I. The furin inhibitor hexa-D-arginine blocks the activation of Pseudomonas aeruginosa exotoxin A in vivo. Infect. Immun. 70, 7136-7139 (2002).
27. Kiefersauer, R. et al. A novel free-mounting system for protein crystals: transformation and improvement of diffraction quality by accurately controlled humidity changes. Appl. Crystallogr. 33, 1223-1230 (2000).
28. Otwinowski, Z. & Minor, W. Processing of X-ray diffraction data collected in oscillations mode. Methods Enzymol. 276, 307-326 (1997).
29. Collaborative Computational Project, Number 4. The CCP4 Suite: Programs for Protein Crystallography. Acta Crystallogr. D 50, 760-763 (1994).
30. Turk, D. Weiterentwicklung eines Programms f_r Molekuelgraphik lund Elektrondichte-Manipulation und seine Anwendung auf verschiedene Protein-Strukturaufklärungen. Dissertation, Technische Universität München (1992).
31. Brünger, A.T. et al. Crystallography and NMR system: a new software suite for macromolecular structure determination. Acta Crystallogr. A 54, 905-921 (1998).
32. Nicholls, A., Bharadwaj, R. & Honig, B. Grasp: graphical representation and analysis of surface properties. Biophys. J. 64, A166 (1993).
33. Esnouf, R.M. Further additions to MolScript version 1.4, including reading and contouring of electron density maps. Acta Crystallogr. D 55, 938-940 (1999).
34. Kraulis, P. J. MolScript: a program to produce both detailed and schematic plots of protein structures. J. Appl. Crystallogr. 24, 946-950 (1991).
35. Merritt, E.A. & Bacon, D.J. Raster3D: photorealistic molecular graphics. Methods Enzymol. 277, 505-524 (1997).
36. Barton, G.J. ALSCRIPT: a tool to format multiple sequence alignments. Protein Eng. 6, 37-40 (1993).