Recognition of protein substrates by the prolyl isomerase trigger factor is independent of proline residues

Journal of Molecular Biology
Christian ScholzF X Schmid

Abstract

The trigger factor is associated with bacterial ribosomes and catalyzes proline-limited protein folding reactions. Its folding activity is very high and conserved in evolution, as shown for the homologous enzymes from Escherichia coli and Mycoplasma genitalium. The folding protein substrate (a variant of ribonuclease T1) binds with high affinity to the trigger factors, and permanently unfolded proteins are strong, competitive inhibitors. We used this inhibition to characterize the substrate binding sites of the trigger factors. Unfolded alpha-lactalbumin binds very tightly and inhibits the trigger factor from M. genitalium with a KI value of 50 nM. The binding of inhibitory proteins is independent of proline residues, as shown for unfolded tendamistat, which binds to the trigger factor with equal affinity in the presence and in the absence of its three proline residues. The good inhibition by a non-folding variant of ribonuclease T1 that lacks Pro39 showed that this proline, at which the catalysis of folding occurs, is dispensable for substrate binding. The trigger factors cannot catalyze prolyl isomerization when proteins are partially folded already. They preferentially recognize unstructured protein chains, which bind with h...Continue Reading

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Citations

Nov 19, 2009·Proceedings of the National Academy of Sciences of the United States of America·Roman P JakobFranz X Schmid
Mar 4, 2000·Applied and Environmental Microbiology·K NishiharaT Yura
Jun 8, 2001·Annual Review of Biochemistry·J Frydman
Nov 28, 2002·Biological Chemistry·Holger PatzeltElke Deuerling
Jan 30, 2003·Biological Chemistry·Cordelia Schiene-FischerGunter Fischer
Sep 9, 2004·Proceedings of the National Academy of Sciences of the United States of America·Anthony V LudlamZhaohui Xu
Nov 29, 2001·Proceedings of the National Academy of Sciences of the United States of America·H PatzeltE Deuerling
Aug 26, 2006·Molecular Microbiology·Gunter Fischer, Stephan Wawra
Sep 4, 2014·Microbiology and Molecular Biology Reviews : MMBR·Can M Ünala, Michael Steinert
Mar 11, 2000·European Journal of Biochemistry·V C WasingerI Humphery-Smith
Sep 17, 2002·European Journal of Biochemistry·Guo-Chang HuangJun-Mei Zhou
Nov 7, 2003·The Journal of Biological Chemistry·Ryoji SunoMasasuke Yoshida
Feb 14, 2007·The Journal of Biological Chemistry·Sathish K LakshmipathyStephanie A Etchells
Feb 5, 1999·Journal of Molecular Biology·A JabsR Hilgenfeld
Jan 4, 2006·Biochemistry·Christian ScholzFranz Xaver Schmid
Jul 10, 2003·Chemical Reviews·Christophe Dugave, Luc Demange
Dec 15, 2010·Journal of Molecular Biology·Gabriel Zoldák, Franz X Schmid

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