Structural stabilization of botulinum neurotoxins by tyrosine phosphorylation

FEBS Letters
J A EncinarA Ferrer-Montiel

Abstract

Tyrosine phosphorylation of botulinum neurotoxins augments their proteolytic activity and thermal stability, suggesting a substantial modification of the global protein conformation. We used Fourier-transform infrared (FTIR) spectroscopy to study changes of secondary structure and thermostability of tyrosine phosphorylated botulinum neurotoxins A (BoNT A) and E (BoNT E). Changes in the conformationally-sensitive amide I band upon phosphorylation indicated an increase of the alpha-helical content with a concomitant decrease of less ordered structures such as turns and random coils, and without changes in beta-sheet content. These changes in secondary structure were accompanied by an increase in the residual amide II absorbance band remaining upon H-D exchange, consistent with a tighter packing of the phosphorylated proteins. FTIR and differential scanning calorimetry (DSC) analyses of the denaturation process show that phosphorylated neurotoxins denature at temperatures higher than those required by non-phosphorylated species. These findings indicate that tyrosine phosphorylation induced a transition to higher order and that the more compact structure presumably imparts to the phosphorylated neurotoxins the higher catalytic acti...Continue Reading

References

Nov 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·A V Ferrer-MontielM Montal
Jan 1, 1990·Annual Review of Biophysics and Biophysical Chemistry·E FreireJ M Sanchez-Ruiz
Jan 1, 1988·Annual Review of Biophysics and Biophysical Chemistry·M S Braiman, K J Rothschild
Jan 1, 1986·Advances in Protein Chemistry·S Krimm, J Bandekar
Jun 1, 1969·Journal of Bacteriology·M KitamuraG Sakaguchi
Jul 1, 1994·Molecular Microbiology·C Montecucco, G Schiavo
May 1, 1995·Progress in Neurobiology·G Ahnert-Hilger, H Bigalke
Apr 21, 1995·The Journal of Biological Chemistry·S BañuelosG Pifat
Jun 6, 1994·FEBS Letters·C MontecuccoG Schiavo
Jan 1, 1994·Annual Review of Neuroscience·R Jahn, T C Südhof
Jan 1, 1993·Annual Review of Biophysics and Biomolecular Structure·L N Johnson, D Barford
Aug 2, 1996·The Journal of Biological Chemistry·A V Ferrer-MontielM Montal
Aug 1, 1996·Current Opinion in Structural Biology·A Shaw, R Bott

❮ Previous
Next ❯

Citations

Feb 24, 2009·Analytical and Bioanalytical Chemistry·Fang Wei, Chih-Ming Ho
Sep 9, 2000·Toxicon : Official Journal of the International Society on Toxinology·M AdlerS S Deshpande
Nov 6, 2002·Trends in Biochemical Sciences·Kathryn TurtonK Ravi Acharya
Sep 22, 2006·Infection and Immunity·Fang CaiJames E Keller
Dec 8, 2004·FEBS Letters·Cristina IbañezAntonio Ferrer-Montiel
Apr 21, 2004·Protein Science : a Publication of the Protein Society·Frederico Faria MirandaAurora Martínez
Oct 28, 2017·Molecular Biology of the Cell·Sunandini ChandraDebi P Sarkar
Nov 1, 2000·The Journal of Biological Chemistry·J A EncinarJ L Iovanna
Jan 14, 2004·Biochemistry·James E KellerElaine A Neale
Aug 21, 2003·Annales de réadaptation et de médecine physique : revue scientifique de la Société française de rééducation fonctionnelle de réadaptation et de médecine physique·B Poulain, Y Humeau

❮ Previous
Next ❯

Related Concepts

Related Feeds

Botulism (ASM)

Botulism is a rare but serious paralytic illness caused by a nerve toxin that is produced by the bacterium clostridium botulinum. Discover the latest research on botulism here.

Botulism

Botulism is a rare but serious paralytic illness caused by a nerve toxin that is produced by the bacterium clostridium botulinum. Discover the latest research on botulism here.