Structural analysis of asparaginyl endopeptidase reveals the activation mechanism and a reversible intermediate maturation stage

Cell Research

Volumn 24, Issue 3, 2014, Pages 344-358

  Zhao, Lixia ^a,b   Hua, Tian ^a   Crowley, Christopher ^c   Ru, Heng ^a   Ni, Xiangmin ^a   Shaw, Neil ^a   Jiao, Lianying ^a   Ding, Wei ^a   Qu, Lu ^a   Hung, Li Wei ^d   Huang, Wei ^b   Liu, Lei ^e   Ye, Keqiang ^f   Ouyang, Songying ^a   Cheng, Genhong ^c   Liu, Zhi Jie ^a,b  

^a INSTITUTE OF BIOPHYSICS   (China)

^b SHANGHAITECH UNIVERSITY   (China)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d LOS ALAMOS NATIONAL LABORATORY   (United States)

^e TSINGHUA UNIVERSITY   (China)

^f EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

asparaginyl endopeptidase; autoproteolytic maturation; crystal structure; innate immunity

Indexed keywords

CATHEPSIN; CYSTATIN C; CYSTEINE PROTEINASE; ENZYME PRECURSOR; LEGUMAIN; PROTEIN BINDING;

AMINO ACID SEQUENCE; ANIMAL; BINDING SITE; CHEMISTRY; ENZYME ACTIVE SITE; ENZYME SPECIFICITY; GENETICS; HEK293 CELL LINE; HUMAN; METABOLISM; MOLECULAR DYNAMICS; MOLECULAR GENETICS; MOUSE; PH; PROTEIN TERTIARY STRUCTURE; SEQUENCE ALIGNMENT; SITE DIRECTED MUTAGENESIS; X RAY CRYSTALLOGRAPHY;

AMINO ACID SEQUENCE; ANIMALS; BINDING SITES; CATALYTIC DOMAIN; CATHEPSINS; CRYSTALLOGRAPHY, X-RAY; CYSTATIN C; CYSTEINE ENDOPEPTIDASES; ENZYME PRECURSORS; HEK293 CELLS; HUMANS; HYDROGEN-ION CONCENTRATION; MICE; MOLECULAR DYNAMICS SIMULATION; MOLECULAR SEQUENCE DATA; MUTAGENESIS, SITE-DIRECTED; PROTEIN BINDING; PROTEIN STRUCTURE, TERTIARY; SEQUENCE ALIGNMENT; SUBSTRATE SPECIFICITY;

EID: 84897632293     PISSN: 10010602     EISSN: 17487838     Source Type: Journal    
DOI: 10.1038/cr.2014.4     Document Type: Article

References (48)

1. Chen JM, Dando PM, Rawlings ND, et al. Cloning, isolation, and characterization of mammalian legumain, an asparaginyl endopeptidase. J Biol Chem 1997; 272:8090-8098.
2. Chen JM, Dando PM, Stevens RA, Fortunato M, Barrett AJ. Cloning and expression of mouse legumain, a lysosomal endopeptidase. Biochem J 1998; 335:111-117.
3. Chen JM, Rawlings ND, Stevens RA, Barrett AJ. Identification of the active site of legumain links it to caspases, clostripain and gingipains in a new clan of cysteine endopeptidases. FEBS Lett 1998; 441:361-365.
4. Chan CB, Abe M, Hashimoto N, et al. Mice lacking asparaginyl endopeptidase develop disorders resembling hemophagocytic syndrome. Proc Natl Acad Sci USA 2009; 106:468-473.
5. Morita Y, Araki H, Sugimoto T, et al. Legumain/asparaginyl endopeptidase controls extracellular matrix remodeling through the degradation of fibronectin in mouse renal proximal tubular cells. FEBS Lett 2007; 581:1417-1424.
6. Chen JM, Fortunato M, Stevens RA, Barrett AJ. Activation of progelatinase A by mammalian legumain, a recently discovered cysteine proteinase. Biol Chem 2001; 382:777-783.
7. Sarandeses CS, Covelo G, Diaz-Jullien C, Freire M. Prothymosin alpha is processed to thymosin alpha 1 and thymosin alpha 11 by a lysosomal asparaginyl endopeptidase. J Biol Chem 2003; 278:13286-13293.
8. Alvarez-Fernandez M, Barrett AJ, Gerhartz B, et al. Inhibition of mammalian legumain by some cystatins is due to a novel second reactive site. J Biol Chem 1999; 274:19195-19203.
9. Hsing LC, Rudensky AY. The lysosomal cysteine proteases in MHC class II antigen presentation. Immunol Rev 2005; 207:229-241.
10. Manoury B, Hewitt EW, Morrice N, et al. An asparaginyl endopeptidase processes a microbial antigen for class II MHC presentation. Nature 1998; 396:695-699.
11. Antoniou AN, Blackwood SL, Mazzeo D, Watts C. Control of antigen presentation by a single protease cleavage site. Immunity 2000; 12:391-398.
12. Ewald SE, Lee BL, Lau L, et al. The ectodomain of Toll-like receptor 9 is cleaved to generate a functional receptor. Nature 2008; 456:658-662.
13. Bauer S. Toll-like receptor 9 processing: the key event in Tolllike receptor 9 activation? Immunol Lett 2013; 149:85-87.
14. Ewald SE, Engel A, Lee J, et al. Nucleic acid recognition by Toll-like receptors is coupled to stepwise processing by cathepsins and asparagine endopeptidase. J Exp Med 2011; 208:643-651.
15. Park B, Brinkmann MM, Spooner E, et al. Proteolytic cleavage in an endolysosomal compartment is required for activation of Toll-like receptor 9. Nat Immunol 2008; 9:1407-1414.
16. Sepulveda FE, Maschalidi S, Colisson R, et al. Critical role for asparagine endopeptidase in endocytic Toll-like receptor signaling in dendritic cells. Immunity 2009; 31:737-748.
17. Saska I, Gillon AD, Hatsugai N, et al. An asparaginyl endopeptidase mediates in vivo protein backbone cyclization. J Biol Chem 2007; 282:29721-29728.
18. Mylne JS, Chan LY, Chanson AH, et al. Cyclic peptides arising by evolutionary parallelism via asparaginyl-endopeptidase-mediated biosynthesis. Plant Cell 2012; 24:2765-2778.
19. Niestroj AJ, Feussner K, Heiser U, et al. Inhibition of mammalian legumain by Michael acceptors and AzaAsn-halomethylketones. Biol Chem 2002; 383:1205-1214.
20. Chen JM, Fortunato M, Barrett AJ. Activation of human prolegumain by cleavage at a C-terminal asparagine residue. Biochem J 2000; 352:327-334.
21. Li DN, Matthews SP, Antoniou AN, Mazzeo D, Watts C. Multistep autoactivation of asparaginyl endopeptidase in vitro and in vivo. J Biol Chem 2003; 278:38980-38990.
22. Dall E, Brandstetter H. Activation of legumain involves proteolytic and conformational events, resulting in a context-and substrate-dependent activity profile. Acta Crystallogr Sect F Struct Biol Cryst Commun 2012; 68:24-31.
23. Holm L, Rosenstrom P. Dali server: conservation mapping in 3D. Nucleic Acids Res 2010; 38:W545-W549.
24. Laskowski RA, Watson JD, Thornton JM. ProFunc: a server for predicting protein function from 3D structure. Nucleic Acids Res 2005; 33:W89-W93.
25. Walters J, Schipper JL, Swartz P, Mattos C, Clark AC. Allosteric modulation of caspase 3 through mutagenesis. Biosci Rep 2012; 32:401-411.
26. Wilson KP, Black JA, Thomson JA, et al. Structure and mechanism of interleukin-1 beta converting enzyme. Nature 1994; 370:270-275.
27. Kuroyanagi M, Nishimura M, Hara-Nishimura I. Activation of Arabidopsis vacuolar processing enzyme by self-catalytic removal of an auto-inhibitory domain of the C-terminal propeptide. Plant Cell Physiol 2002; 43:143-151.
28. Dalboge H, Jensen EB, Tottrup H, et al. High-level expression of active human cystatin C in Escherichia coli. Gene 1989; 79:325-332.
29. Ouyang S, Gong B, Li JZ, et al. Structural insights into a human anti-IFN antibody exerting therapeutic potential for systemic lupus erythematosus. J Mol Med (Berl) 2012; 90:837-846.
30. Hall A, Ekiel I, Mason RW, et al. Structural basis for different inhibitory specificities of human cystatins C and D. Biochemistry 1998; 37:4071-4079.
31. Lutgens SP, Cleutjens KB, Daemen MJ, Heeneman S. Cathepsin cysteine proteases in cardiovascular disease. Faseb J 2007; 21:3029-3041.
32. Dall E, Brandstetter H. Mechanistic and structural studies on legumain explain its zymogenicity, distinct activation pathways, and regulation. Proc Natl Acad Sci USA 2013; 110:10940-10945.
33. Stols L, Zhou M, Eschenfeldt WH, et al. New vectors for coexpression of proteins: structure of Bacillus subtilis ScoAB obtained by high-throughput protocols. Protein Expr Purif 2007; 53:396-403.
34. Liang W, Ouyang S, Shaw N, et al. Conversion of D-ribulose 5-phosphate to D-xylulose 5-phosphate: new insights from structural and biochemical studies on human RPE. Faseb J 2011; 25:497-504.
35. Mori T, Nishizawa S, Hirohashi Y, et al. Efficiency of G2/M-related tumor-associated antigen-targeting cancer immunotherapy depends on antigen expression in the cancer stem-like population. Exp Mol Pathol 2012; 92:27-32.
36. Otwinowski Z, Minor W. Processing of X-ray diffraction data collected in oscillation mode. Methods in Enzymology 1997; 276:307-326.
37. Liu ZJ, Lin D, Tempel W, et al. Parameter-space screening: a powerful tool for high-throughput crystal structure determination. Acta Crystallogr D Biol Crystallogr 2005; 61:520-527.
38. Ru H, Zhao L, Ding W, et al. S-SAD phasing study of death receptor 6 and its solution conformation revealed by SAXS. Acta Crystallogr D Biol Crystallogr 2012; 68:521-530.
39. Hendrickson WA. Determination of macromolecular structures from anomalous diffraction of synchrotron radiation. Science 1991; 254:51-58.
40. Adams PD, Afonine PV, Bunkoczi G, et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr D Biol Crystallogr 2010; 66:213-221.
41. McCoy AJ, Grosse-Kunstleve RW, Adams PD, et al. Phaser crystallographic software. J Appl Crystallogr 2007; 40:658-674.
42. Emsley P, Lohkamp B, Scott WG, Cowtan K. Features and development of Coot. Acta Crystallogr D Biol Crystallogr 2010; 66:486-501.
43. Murshudov GN, Vagin AA, Dodson EJ. Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr D Biol Crystallogr 1997; 53:240-255.
44. Niu F, Shaw N, Wang YE, et al. Structure of the Leanyer orthobunyavirus nucleoprotein-RNA complex reveals unique architecture for RNA encapsidation. Proc Natl Acad Sci USA 2013; 110:9054-9059.
45. Jiao L, Ouyang S, Liang M, et al. Structure of severe fever with thrombocytopenia syndrome virus nucleocapsid protein in complex with suramin reveals therapeutic potential. J Virol 2013; 87:6829-6839.
46. Schmidt B, Konig S, Svergun D, et al. Small-angle X-ray solution scattering study on the dimerization of the FKBP25mem from Legionella pneumophila. FEBS Lett 1995; 372:169-172.
47. Svergun DI, Petoukhov MV, Koch MH. Determination of domain structure of proteins from X-ray solution scattering. Biophys J 2001; 80:2946-2953.
48. Niu F, Ru H, Ding W, Ouyang S, Liu ZJ. Structural biology study of human TNF receptor associated factor 4 TRAF domain. Protein Cell 2013; 4:687-694.