Abstract
Two novel metalloendopeptidases in Arabidopsis thaliana, AtPreP1 and AtPreP2, are responsible for the degradation of targeting peptides in mitochondria and chloroplasts. Both AtPreP1 and AtPreP2 contain ambiguous targeting peptides and are dually targeted to both organelles. The proteases also have the capacity to degrade unstructured peptides of up to 65 amino acid residues, but not small proteins. The catalysis occurs in a huge catalytic chamber revealed by the crystal structure of AtPreP1 at 2.1 Å. The enzymes show a preference for basic and small uncharged amino acids or serines at the cleavage sites. Despite similarities in cleavage specificities, cleavage-site recognition differs for both proteases and is context- and structure-dependent. The AtPreP1 and AtPreP2 genes are differentially expressed in Arabidopsis.
References
Adam, Z. and Clarke, A.K. (2002). Cutting edge of chloroplast proteolysis. Trends Plant Sci.7, 451–456.10.1016/S1360-1385(02)02326-9Search in Google Scholar
Adam, Z., Rudella, A., and van Wijk, K.J. (2006). Recent advances in the study of Clp, FtsH and other proteases located in chloroplasts. Curr. Opin. Plant Biol.9, 234–240.10.1016/j.pbi.2006.03.010Search in Google Scholar
Arnold, I. and Langer, T. (2002). Membrane protein degradation by AAA proteases in mitochondria. Biochim. Biophys. Acta1592, 89–96.10.1016/S0167-4889(02)00267-7Search in Google Scholar
Barrett, A., Rawlings, N., and Woessner, J. (1998). Handbook of Proteolytic Enzymes (London, UK: Academic Press).Search in Google Scholar
Becker, A.B. and Roth, R.A. (1992). An unusual active site identified in a family of zinc metalloendopeptidases. Proc. Natl. Acad. Sci. USA89, 3835–3839.10.1073/pnas.89.9.3835Search in Google Scholar PubMed PubMed Central
Bedard, J. and Jarvis, P. (2005). Recognition and envelope translocation of chloroplast preproteins. J. Exp. Bot.56, 2287–2320.10.1093/jxb/eri243Search in Google Scholar PubMed
Bhushan, S., Lefebvre, B., Stahl, A., Wright, S.J., Bruce, B.D., Boutry, M., and Glaser, E. (2003). Dual targeting and function of a protease in mitochondria and chloroplasts. EMBO Rep.4, 1073–1078.10.1038/sj.embor.7400011Search in Google Scholar
Bhushan, S., Ståhl, A., Nilsson, S., Lefebvre, B., Seki, M., Roth, C., McWilliam, D., Wright J.S., Liberles, A.D., Shinozaki, K., et al. (2005). Catalysis, subcellular localization, expression and evolution of the targeting peptides degrading protease, AtPreP2. Plant Cell Physiol.46, 985–996.10.1093/pcp/pci107Search in Google Scholar PubMed
Bhushan, S., Johnson, K.A., Eneqvist, T., and Glaser, E. (2006). Proteolytic mechanism of a novel mitochondrial and chloroplastic PreP peptidasome. Biol. Chem.387, 1087–1090.10.1515/BC.2006.134Search in Google Scholar PubMed
Buchler, M., Tisljar, U., and Wolf, D.H. (1994). Proteinase yscD (oligopeptidase yscD). Structure, function and relationship of the yeast enzyme with mammalian thimet oilgopeptidase (metalloendopeptidase, EP 24.15). Eur. J. Biochem.219, 627–639.Search in Google Scholar
Caspersen, C., Wang, N., Yao, J., Sosunov, A., Chen, X., Lustbader, J.W., Xu, H.W., Stern, D., McKhann, G., and Yan, S.D. (2005). Mitochondrial Aβ: a potential focal point for neuronal metabolic dysfunction in Alzheimer's disease. FASEB J.19, 2040–2041.10.1096/fj.05-3735fjeSearch in Google Scholar PubMed
Chen, G., Bi, Y.R., and Li, N. (2005). EGY1 encodes a membrane-associated and ATP-independent metalloprotease that is required for chloroplast development. Plant J.41, 264–375.10.1111/j.1365-313X.2004.02308.xSearch in Google Scholar PubMed
Dai, Q.H., Tommos, C., Fuentes, E.J., Blomberg, M.R., Dutton, P.L., and Wand, A.J. (2002). Structure of a de novo designed protein model of radical enzymes. J. Am. Chem. Soc.124, 10952–10953.10.1021/ja0264201Search in Google Scholar
Danpure, C.J. (1995). How can the products of a single gene be localized in more than one intracellular compartment? Trends Cell Biol.5, 230–238.Search in Google Scholar
Duckworth, W.C., Bennett, R.G., and Hamel, F.G. (1998). Insulin degradation: progress and potential. Endocr. Rev.19, 608–624.Search in Google Scholar
Esser, K., Tursun, B., Ingenhoven, M., Michaelis, G., and Pratje, E. (2002). A novel two-step mechanism for removal of a mitochondrial signal sequence involves the mAAA complex and the putative rhomboid protease Pcp1. J. Mol. Biol.323, 835–843.10.1016/S0022-2836(02)01000-8Search in Google Scholar
Falkevall, A., Alikhani, N., Bhushan, S., Pavlov, P.F., Busch, K., Johnson, K.A., Eneqvist, T., Tjernberg, L., Ankarcrona, M., and Glaser, E. (2006). Degradation of the amyloid β-protein by the novel mitochondrial peptidasome, PreP. J. Biol. Chem. July 18; (Epub ahead of print, DOI 10.1074/jbc.M602532200).10.1074/jbc.M602532200Search in Google Scholar PubMed
Glaser, E. and Dessi, P. (1999). Integration of the mitochondrial-processing peptidase into the cytochrome bc1 complex in plants. J. Bioenerg. Biomembr.31, 259–274.10.1023/A:1005475930477Search in Google Scholar
Glaser, E. and Soll, J. (2004). Targeting signals and import machinery of plastids and plant mitochondria. In: Molecular Biology and Biotechnology of Plant Organelles, H. Daniell and C. Chase, eds. (Dordrecht, Netherlands: Springer), pp. 385–418.10.1007/978-1-4020-3166-3_14Search in Google Scholar
Haussuhl, K., Andersson, B., and Adamska, I. (2001). A chloroplast DegP2 protease performs the primary cleavage of the photodamaged D1 protein in plant photosystem II. EMBO J.20, 713–722.Search in Google Scholar
Hedtke, B., Borner, T., and Weihe, A. (2000). One RNA polymerase serving two genomes. EMBO Rep.1, 435–440.10.1093/embo-reports/kvd086Search in Google Scholar PubMed PubMed Central
Johnson, K.A., Bhushan, S., Ståhl, A., Hallberg B.M., Frohn, A., Glaser, E., and Eneqvist, T. (2006). The closed structure of presequence protease prep forms a unique 10.000 Å3 chamber for proteolysis. EMBO J.25, 1977–1986.Search in Google Scholar
Kambacheld, M., Augustin, S., Tatsuta, T., Muller, S., and Langer, T. (2005). Role of a novel metallopeptidase Mop112 and saccharolysin for the complete degradation of proteins residing in different subcompartmnets of mitochondria. J. Biol. Chem.280, 20132–20139.10.1074/jbc.M500398200Search in Google Scholar PubMed
Kaser, M. and Langer, T. (2000). Protein degradation in mitochondria. Semin. Cell Dev. Biol.11, 181–190.10.1006/scdb.2000.0166Search in Google Scholar PubMed
Kaser, M., Kambacheld, M., Kisters-Woike, B., and Langer, T. (2003). Oma1, a novel membrane-bound metallopeptidase in mitochondria with activities overlapping with the m-AAA protease. J. Biol. Chem.278, 46414–46423.10.1074/jbc.M305584200Search in Google Scholar PubMed
Lensch, M., Herrmann, R.G., and Sokolenko, A. (2001). Identification and characterization of SppA, a novel light-inducible chloroplast protease complex associated with thylakoid membranes. J. Biol. Chem.276, 33645–33651.10.1074/jbc.M100506200Search in Google Scholar PubMed
Lister, R., Murcha, M.W., and Whelan, J. (2003). The Mitochondrial Protein Import Machinery of Plants (MPIMP) database. Nucleic Acids Res.31, 325–327.10.1093/nar/gkg055Search in Google Scholar
Lister, R., Chew, O., Lee, M.N., Heazlewood, J.L., Clifton, R., Parker, K.L., Millar, A.H., and Whelan, J. (2004). A transcriptomic and proteomic characterization of the Arabidopsis mitochondrial protein import apparatus and its response to mitochondrial dysfunction. Plant Physiol.134, 777–789.10.1104/pp.103.033910Search in Google Scholar
Lustbader, J.W., Cirilli, M., Lin, C., Xu, H.W., Takuma, K., Wang, N., Caspersen, C., Chen, X., Pollak, S., Chaney, M., et al. (2004). ABAD directly links Aβ to mitochondrial toxicity in Alzheimer's disease. Science304, 448–452.10.1126/science.1091230Search in Google Scholar
Moberg, P., Stahl, A., Bhushan, S., Wright, S.J., Eriksson, A., Bruce, B.D., and Glaser, E. (2003). Characterization of a novel zinc metalloprotease involved in degrading targeting peptides in mitochondria and chloroplasts. Plant J.36, 616–628.10.1046/j.1365-313X.2003.01904.xSearch in Google Scholar
Moberg, P., Nilsson, S., Stahl, A., Eriksson, A.C., Glaser, E., and Maler, L. (2004). NMR solution structure of the mitochondrial F1β presequence from Nicotiana plumbaginifolia. J. Mol. Biol.336, 1129–1140.10.1016/j.jmb.2004.01.006Search in Google Scholar
Neupert, W. and Brunner, M. (2002). The protein import motor of mitochondria. Nat. Rev. Mol. Cell Biol.3, 555–565.10.1038/nrm878Search in Google Scholar
Nicolay, K., Laterveer, F., and Heerde, W. (1994). Effects of amphipathic peptides, including presequences, on the functional integrity of rat liver mitochondrial membranes. J. Bioenerg. Biomembr.26, 327–334.10.1007/BF00763104Search in Google Scholar
Pavlov, P.F., Moberg, P., Zhang, X.P., and Glaser, E. (1999). Chemical cleavage of the overexpressed mitochondrial F1β precursor with CNBr: a new strategy to construct an import-competent preprotein. Biochem. J.341, 95–103.10.1042/bj3410095Search in Google Scholar
Peeters, N. and Small, I. (2001). Dual targeting to mitochondria and chloroplasts. Biochim. Biophys. Acta1541, 54–63.10.1016/S0167-4889(01)00146-XSearch in Google Scholar
Richter, S. and Lamppa, G.K. (1998). A chloroplast processing enzyme functions as the general stromal processing peptidase. Proc. Natl. Acad. Sci. USA95, 7463–7468.10.1073/pnas.95.13.7463Search in Google Scholar PubMed PubMed Central
Rudhe, C., Chew, O., Whelan, J., and Glaser, E. (2002). A novel in vitro system for simultaneous import of precursor proteins into mitochondria and chloroplasts. Plant J.30, 213–220.10.1046/j.1365-313X.2002.01280.xSearch in Google Scholar
Silva-Filho, M.C. (2003). One ticket for multiple destinations: dual targeting of proteins to distinct subcellular locations. Curr. Opin. Plant Biol.6, 589–595.10.1016/j.pbi.2003.09.008Search in Google Scholar
Skelton, N.J., Kordel, J., and Chazin, W.J. (1995). Determination of the solution structure of Apo calbindin D9k by NMR spectroscopy. J. Mol. Biol.249, 441–462.10.1006/jmbi.1995.0308Search in Google Scholar
Small, I., Wintz, H., Akashi, K., and Mireau, H. (1998). Two birds with one stone: genes that encode products targeted to two or more compartments. Plant Mol. Biol.38, 265–277.10.1023/A:1006081903354Search in Google Scholar
Sokolenko, A., Pojidaeva, E., Zinchenko, V., Panichkin, V., Glaser, V.M., Herrmann, R.G., and Shestakov, S.V. (2002). The gene complement for proteolysis in the cyanobacterium Synechocystis sp. PCC 6803 and Arabidopsis thaliana chloroplasts. Curr. Genet.41, 291–310.Search in Google Scholar
Stahl, A., Pavlov, P., and Glaser, E. (2000). Rapid degradation of the presequence of the F1β subunit of the ATP synthase inside mitochondria. Biochem. J.369, 703–707.10.1042/bj3490703Search in Google Scholar
Stahl, A., Moberg, P., Ytterberg, J., Panfilov, O., Brockenhuus Von Lowenhielm, H., Nilsson, F., and Glaser, E. (2002). Isolation and identification of a novel mitochondrial metalloprotease (PreP) that degrades targeting presequences in plants. J. Biol. Chem.277, 41931–41939.10.1074/jbc.M205500200Search in Google Scholar
Stahl, A., Nilsson, S., Lundberg, P., Bhushan, S., Biverstahl, H., Moberg, P., Morisset, M., Vener, A., Maler, L., Langel, U., and Glaser, E. (2005). Two novel targeting peptide degrading proteases, PrePs, in mitochondria and chloroplasts, so similar and still different. J. Mol. Biol.349, 847–860.10.1016/j.jmb.2005.04.023Search in Google Scholar
Vajdos, F.F., Ultsch, M., Schaffer, M.L., Deshayes, K.D., Liu, J., Skelton, N.J., and de Vos, A.M. (2001). Crystal structure of human insulin-like growth factor-1: detergent binding inhibits binding protein interactions. Biochemistry40, 11022–11029.10.1021/bi0109111Search in Google Scholar
Van der Bliek, A.M. and Koehler, C.M. (2003). A mitochondrial rhomboid protease. Dev. Cell4, 769–770.10.1016/S1534-5807(03)00167-9Search in Google Scholar
Wieprecht, T., Apostolov, O., Beyermann, M., and Seelig, J. (2000). Interaction of a mitochondrial presequence with lipid membranes: role of helix formation for membrane binding and perturbation. Biochemistry19, 15297–15305.10.1021/bi001774vSearch in Google Scholar PubMed
Zhang, X.P. and Glaser, E. (2002). Interaction of plant mitochondrial and chloroplast signal peptides with the Hsp70 molecular chaperone. Trends Plant Sci.7, 14–21.10.1016/S1360-1385(01)02180-XSearch in Google Scholar
©2006 by Walter de Gruyter Berlin New York