Director, Mass Spectrometry LaboratoryDepartment of Biochemistry and Molecular Biology
University of Kansas Medical Center
(913) 588-3487
aartigues@kumc.edu
Newly made proteins must achieve their native configuration before they can play their physiological roles in the cell. These processes are of particular importance for mitochondria. Of the roughly 1100 different proteins present in the mitochondrion only 13 are encoded by the mitochondrial DNA and synthesized in the mitochondrial matrix. The remaining proteins are encoded by the nuclear genome, transcribed in the nucleus, translated in the cytoplasm and imported into the mitochondrion, where they fold to their native structure. Understanding these processes at the molecular level is of the utmost importance because alterations in protein folding or mitochondrial protein translocation cause disease.
The model system used to study this process is the eukaryotic isoenzymes of aspartate aminotransferase. Two isoenzymes, one cytosolic, the other mitochondrial, exist in all eukaryotic cells. These proteins have extensive amino acid similarity, an almost identical three dimensional structure, are encoded by the genomic DNA, and are synthesized in the cytoplasm. Despite these similarities the mature proteins have different folding kinetics and different sub-cellular locations. Our main goals are to understand; (a) the molecular basis for the distinct folding behavior of these homologous proteins, and (b) to elucidate the mechanisms for the differences observed in their interactions with the cellular machineries in charge of protein sorting, import and folding.
J. A. Oses-Prieto, M.T. Bengoechea-Alonso, A. Arftigues, A. Iriarte, and M. Martinez-Carrion: On the nature of the rate-limiting steps in the refolding of the cofactor-dependent protein aspartate aminotransferase. J. Biol. Chem. 278:49988-4999 (2003).
A. Artigues, A. Iriarte and M. Martinez-Carrion: Binding to Chaperones allows import of a purified mitochondrial precursor into mitochondria. J. Biol. Chem. 277:25047-25055 (2002).
J.P. Gorski, F.-T., Liu, A. Artigues, L.F. Castagana, and P. Osdoby: New Alternatively Spliced Form of Galectin-3, a Member of alpha-Galactoside-Binding Animal Lectin Family, Contains Predicted Transmembrane Spanning Domain and Leucine Zipper Motif, J. Biol. Chem., 277:18840-18848 (2002).
Martinez-Carrion, M., Oses-Prieto, J.A., Bengoechea-Alonso, M.T., Artigues, A. and Iriarte, A., The Role of Pyridoxal Phosphate in the Folding of Mitochondrial Aspartate Aminotransferase: a Mass Spectroscopic Analysis" 3rd International Symposium on Vitamin B6, PQQ, Carbonyl Catalysis and Quinoproteins, Southampton, UK, April 14-19, 2002.
A. Artigues, M. Benogechea-Alonso, D.L. Crawford, A. Iriarte, and Martinez-Carrion, M, Biological implications of the different Hsp 70 binding properties of mitochondrial and cytosolic aspartate aminotransferase In Biochemistry and Molecular Biology of vitamin B6 and PQQ-dependent proteins. a. Iriarte, H.M. Kagan and M. Martinez-Carion (eds.) Birkäuser Verlag Basel/Switzerland pp 111-116 (2000).
A. Artigues, D. L. Crawford, A. Iriarte and M. Martinez-Carrion: Divergent Hsc 70-binding properties of mitochondrial and cytosolic aspartate aminotransferase. Implications for their segregation to different cellular compartments. J. Biol. Chem. 273:33130-33134 (1998)
F. Donate, A. Artigues, A. Iriarte, and M. Martinez-Carrion: Opposite behavior of two isozymes when refolding in the presence of non-ionic detergents. Protein Science 7:1911-1820 (1998)
C. Torella, J. R. Mattingly, Jr., A. Artigues, A. Iriarte, and M. Martinez-Carrion: Insight into the conformation of folding intermediates of a protein trapped by GroEL. J. Biol. Chem. 273:3915-3925 (1998)
A. Artigues, A. Iriarte and Martinez-Carrion: Mapping the hsp 70 binding sites on a large mitochondrial precursor protein. In Techniques in Protein Chemistry VIII, D.R. Marshak (editor). Academic Press, pp 481-492 (1997).
A. Artigues, A. Iriarte and M. Martinez-Carrion: Refolding intermediates of acid-unfolded mitochondrial aspartate aminotransferase bind to Hsc70. J. Biol. Chem. 272:16852-1861 (1997).
J. P. Gorsky, E. Kremer, J. Ruiz-Perez, G. E. Wise, and A. Artigues: Conformational analyses on soluble surface bound osteopontin. Ann N.Y. Acad Sci USA (1995) 760:12-23.
A. Artigues, A. Iriarte and M. Martinez-Carrion: Acid-induced reversible unfolding of mitochondrial aspartate aminotransferase. J. Biol. Chem. 269, 21990-21999 (1994).
A. Iriarte, A. Artigues, B. Lain, J. R. Mattingly, Jr. and M. Martinez-Carrion: Cytosolic factors and the twisting path from birth to berth in aspartate aminotransferases. In Biochemistry of Vitamin B6. G. Marino, G. Sannia and F. Bossa (eds.) Birkäuser Verlag Basel/Switzerland, pp 75-80(1994).
A. Artigues, H. Farrant and V. Schirch: Role of the amino terminal region of serine hydroxymethyltransferase in determining its in vivo rate of turnover. J. Biol. Chem. 268, 13784-13790 (1993).
A. Artigues, A. Birkett and S. Verne: Evidence for the in vivo deamidation and isomerization of an asparaginyl residue in cytosolic serine hydroxymethyltransferase. J. Biol. Chem. 265, 4853-4858 (1990).
A. Artigues, M. T. Villar, A. Fernandez, J. A. Ferragut, and J. M. Gonzlez‑Ros: Cholesterol modulates structural features of the nicotinic acetylcholine receptor in model reconstituted vesicles. Biochem. Biochim. Acta 985, 325-330 (1989).
M. T. Villar, A. Artigues, J. A. Ferragut and J. M. González-Ros: Phospholipase A2 hydrolysis products as membrane specific perturbants to probe structural features of nicotinic acetylcholine receptor. Biochem. Biochim. Acta. 938, 35-43 (1988).
A. Artigues, M. T. Villar, J. A. Ferragut and J. M. González-Ros: Thermal perturbation studies of membrane‑bound acetylcholine receptor from Torpedo: Effects of cholinergic ligands and membrane perturbants. Arch. Biochem. Biopsy. 258, 33-41 (1987).
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