Structural changes induced by the deamidation and isomerization of asparagine revealed by the crystal structure of Ustilago sphaerogena ribonuclease U2B

Biopolymers
Shuji Noguchi

Abstract

Under physiological conditions, the deamidation and isomerization of asparagine to isoaspartate (isoAsp) proceeds nonenzymatically via succinimide. Although a large number of proteins have been reported to contain isoAsp, information concerning the three-dimensional structure of proteins containing isoaspartate is still limited. We have crystallized isoAsp containing Ustilago sphaerogena ribonuclease U2B, and determined the crystal structure at 1.32 Å resolution. The structure revealed that the formation of isoAsp32 induces a single turn unfolding of the α-helix from Asp29 to Asp34, and the region from Asp29 to Arg35 forms a U-shaped loop structure. The electron density map shows that isoAsp32 retained the L-configuration at the C(α) atom. IsoAsp32 is in gauche conformation about a C(α)--C(β) bond, and the polypeptide chain bends by ∼90° at isoAsp32. IsoAsp32 protrudes from the surface of the protein, and the abnormal β-peptide bond in the main-chain and α-carboxylate in the side-chain is fully exposed. The structure suggests that the deamidation of the Asn and the isoAsp formation in proteins could confer immunogenicity.

References

Nov 15, 1986·The Biochemical Journal·S Kanaya, T Uchida
Jun 10, 1997·Proceedings of the National Academy of Sciences of the United States of America·E KimS G Young
Jun 10, 1998·Biochemical and Biophysical Research Communications·D J WeberB Caughey
Apr 28, 1999·Journal of Bacteriology·C L DavidD W Aswad
Jul 31, 1999·The Journal of Biological Chemistry·M J MamulaP R Blier
Apr 20, 2000·Acta Crystallographica. Section D, Biological Crystallography·U ResterW Bode
Jun 8, 2000·Proteins·S Eschenburg, E Schönbrunn
Oct 14, 2000·Archives of Biochemistry and Biophysics·T ShimizuT Shirasawa
Jan 31, 2003·Proteins·Simon C LovellDavid C Richardson
Sep 1, 1994·Acta Crystallographica. Section D, Biological Crystallography·UNKNOWN Collaborative Computational Project, Number 4
May 1, 1997·Acta Crystallographica. Section D, Biological Crystallography·G N MurshudovE J Dodson
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Paul Emsley, Kevin Cowtan
Feb 18, 2005·Proteomics·Xianquan ZhanDominic M Desiderio
Oct 4, 2006·The Journal of Biological Chemistry·Flavio CurnisAngelo Corti
Jun 27, 2007·The Journal of Cell Biology·Seiichiro TakahashiReinhard Fässler
Oct 13, 2009·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Lawrence W DickKuang-Chuan Cheng
Feb 10, 2010·Pharmaceutical Research·Mark Cornell ManningDerrick S Katayama
Jan 1, 1997·Methods in Enzymology·Zbyszek Otwinowski, Wladek Minor

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Citations

Jul 9, 2011·Analytical Chemistry·Nadezda P SargaevaPeter B O'Connor
Jul 21, 2016·Journal of Immunology Research·Anshu KuriakosePradip Nair
Apr 18, 2015·PloS One·Ignacio de la Mora-de la MoraJesús Oria-Hernández
May 13, 2017·Biochemistry·Hanliu WangMichael L Gross
Feb 26, 2019·The Journal of Biological Chemistry·Yana A LyonRyan R Julian
Apr 26, 2014·The Journal of Biological Chemistry·Alexander N PatanananSteven G Clarke
Jan 18, 2017·Science Advances·Christian RothNorbert Sträter
Dec 16, 2020·Annual Review of Physical Chemistry·Marc A Sprague-PiercyRachel W Martin
Feb 25, 2017·Journal of Proteome Research·Yana A LyonRyan R Julian
Sep 10, 2019·Analytical Chemistry·Dylan L RiggsRyan R Julian

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