Single proline residues can dictate the oxidative folding pathways of cysteine-rich peptides

Journal of Molecular Biology
Cyril BoulègueLuis Moroder

Abstract

The cysteine-rich N and C-terminal domains of minicollagen-1 from Hydra nematocysts fold with excesses of oxidized/reduced glutathione (10:1) into globular structures with distinct cystine frameworks despite their identical cysteine sequence pattern. An additional main difference is the cis conformation of a conserved proline residue in the N-terminal and the trans conformation of this residue in the C-terminal domain. Comparative analysis of the oxidative folding revealed for the C-terminal domain a fast and highly cooperative formation of a single disulfide isomer. Conversely, oxidation of the N-terminal domain proceeds mainly via an intermediate that results from the fast quasi-stochastic disulfide formation according to the proximity rule. The rate of conversion of the bead-like isomer into the globular end-product is largely dominated by the trans-to-cis isomerization of the critical proline residue as well assessed by its replacement with (4R)- and (4S)-fluoroproline known to exhibit distinct propensities for the trans and cis conformation, respectively. Independently, whether the trans or cis conformation is favored by these substitutions, both analogues retain sufficient sequence-encoded information to fold almost quant...Continue Reading

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Citations

Oct 27, 2007·Antioxidants & Redox Signaling·Cyril BoulègueLuis Moroder
Mar 1, 2012·Progress in Nuclear Magnetic Resonance Spectroscopy·Julianne L Kitevski-LeBlanc, R Scott Prosser
Mar 18, 2015·Journal of Peptide Science : an Official Publication of the European Peptide Society·Sonja A Dames
Mar 8, 2016·Traffic·Lars EllgaardIneke Braakman
Apr 29, 2009·Biopolymers·Pedro Da SilvaAgnès F Delmas
Apr 20, 2010·Organic & Biomolecular Chemistry·Jari J KoivistoAri M P Koskinen
Jul 3, 2015·Angewandte Chemie·Amelie L BartuschatMarkus R Heinrich
Mar 18, 2021·Beilstein Journal of Organic Chemistry·Vladimir KubyshkinNediljko Budisa
Jul 1, 2007·Journal of Chemical Theory and Computation·M ChinchioH A Scheraga
Oct 22, 2010·Journal of the American Chemical Society·Bastian Holzberger, Andreas Marx
Sep 21, 2006·Journal of the American Chemical Society·Devan Naduthambi, Neal J Zondlo

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