Structural and Functional Characterization of an Ancient Bacterial Transglutaminase Sheds Light on the Minimal Requirements for Protein Cross-Linking

Biochemistry
Catarina G FernandesAdriano O Henriques

Abstract

Transglutaminases are best known for their ability to catalyze protein cross-linking reactions that impart chemical and physical resilience to cellular structures. Here, we report the crystal structure and characterization of Tgl, a transglutaminase from the bacterium Bacillus subtilis. Tgl is produced during sporulation and cross-links the surface of the highly resilient spore. Tgl-like proteins are found only in spore-forming bacteria of the Bacillus and Clostridia classes, indicating an ancient origin. Tgl is a single-domain protein, produced in active form, and the smallest transglutaminase characterized to date. We show that Tgl is structurally similar to bacterial cell wall endopeptidases and has an NlpC/P60 catalytic core, thought to represent the ancestral unit of the cysteine protease fold. We show that Tgl functions through a unique partially redundant catalytic dyad formed by Cys116 and Glu187 or Glu115. Strikingly, the catalytic Cys is insulated within a hydrophobic tunnel that traverses the molecule from side to side. The lack of similarity of Tgl to other transglutaminases together with its small size suggests that an NlpC/P60 catalytic core and insulation of the active site during catalysis may be essential requi...Continue Reading

References

Jul 19, 1994·Proceedings of the National Academy of Sciences of the United States of America·V C YeeD C Teller
Jul 1, 1994·Protein Science : a Publication of the Protein Society·L C PedersenR E Stenkamp
Sep 5, 1993·Journal of Molecular Biology·L Holm, C Sander
Aug 6, 1998·Bioscience, Biotechnology, and Biochemistry·K KobayashiS Yamanaka
Oct 29, 1998·Molecular Microbiology·P PfisterT Leisinger
Feb 11, 1999·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·L PireddaM Piacentini
Aug 19, 1999·Protein Science : a Publication of the Protein Society·K S MakarovaE V Koonin
Dec 12, 2001·Neurochemistry International·Soo Youl KimPeter M Steinert
Feb 28, 2002·Proceedings of the National Academy of Sciences of the United States of America·Shenping LiuJon Clardy
Sep 11, 2002·The Journal of Biological Chemistry·Tatsuki KashiwagiEi-ichiro Suzuki
Oct 9, 2002·The Biochemical Journal·Martin GriffinCarlo M Bergamini
Dec 27, 2002·The Journal of General and Applied Microbiology·Katsunori KobayashiShigeru Yamanaka
Jan 31, 2003·Proteins·Simon C LovellDavid C Richardson
Feb 4, 2003·Nature Reviews. Molecular Cell Biology·Laszlo Lorand, Robert M Graham
Apr 8, 2003·The Journal of Biological Chemistry·Bijan AhvaziPeter M Steinert
Jul 19, 2003·European Journal of Biochemistry·J ZotzelH-L Fuchsbauer
Oct 2, 2003·European Journal of Biochemistry·Jens ZotzelHans-Lothar Fuchsbauer
Jun 3, 2004·Genome Research·Gavin E CrooksSteven E Brenner
Jul 21, 2004·Journal of Computational Chemistry·Chris OostenbrinkWilfred F van Gunsteren
Aug 20, 2004·Journal of Bacteriology·Katerina Ragkousi, Peter Setlow
Mar 5, 2005·Progress in Experimental Tumor Research·Zoltán NemesLászló Fésüs
Mar 8, 2005·Biochemical Pharmacology·Thomas M JeitnerArthur J L Cooper
Nov 4, 2005·Journal of Bacteriology·Rita ZilhãoAdriano O Henriques
Sep 5, 2006·Journal of Bacteriology·Teresa CostaAdriano O Henriques
Nov 24, 2007·Annual Review of Microbiology·Adriano O Henriques, Charles P Moran
Dec 21, 2007·PLoS Biology·Daniel M PinkasChaitan Khosla
Oct 24, 2009·Protein Engineering, Design & Selection : PEDS·Uno TagamiTakatsugu Hirokawa
Jan 9, 2010·Acta Crystallographica. Section D, Biological Crystallography·Vincent B ChenDavid C Richardson
Jan 5, 2011·The Journal of Biological Chemistry·Ming-Te YangTienHsiung Thomas Li
Oct 22, 2011·Biochimica Et Biophysica Acta·Soner GundemirGail V W Johnson
Aug 30, 2012·Nature Methods·Caroline A SchneiderKevin W Eliceiri
Sep 27, 2012·Protein Science : a Publication of the Protein Society·Cornelius Klöck, Chaitan Khosla
Feb 12, 2013·Journal of Bacteriology·Ana B AbecasisAdriano O Henriques

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Citations

May 2, 2018·Journal of Bacteriology·Catarina G FernandesAdriano O Henriques
Jul 29, 2017·The Journal of Biological Chemistry·Wojtek SteffenMichael Schraeml
Jan 4, 2020·World Journal of Microbiology & Biotechnology·Lovaine DuarteMarco Antônio Záchia Ayub
Jun 28, 2020·Molecular Microbiology·Carolina FreitasAdriano O Henriques
May 27, 2016·Microbiology Spectrum·Adam Driks, Patrick Eichenberger

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