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Dames, S.A.

One short cysteine-rich sequence pattern - two different disulfide-bonded structures - a molecular dynamics simulation study.

J. Pept. Sci. 21, 480-494 (2015)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
The nematocyst walls of Hydra are formed by proteins containing small cysteine-rich domains (CRDs) of ~25 amino acids. The first CRD of nematocyst outer all antigen (NW1) and the C-terminal CRD of minicollagen-1 (Mcol1C) contain six cysteines at identical sequence positions, however adopt different disulfide bonded structures. NW1 shows the disulfide connectivities C2-C14/C6-C19/C10-C18 and Mcol1C C2-C18/C6-C14/C10-C19. To analyze if both show structural preferences in the open, non-disulfide bonded form, which explain the formation of either disulfide connectivity pattern, molecular dynamics (MD) simulations at different temperatures were performed. NW1 maintained in the 100-ns MD simulations at 283 K a rather compact fold that is stabilized by specific hydrogen bonds. The Mcol1C structure fluctuated overall more, however stayed most of the time also rather compact. The analysis of the backbone Φ/ψ angles indicated different turn propensities for NW1 and Mcol1C, which mostly can be explained based on published data about the influence of different amino acid side chains on the local backbone conformation. Whereas a folded precursor mechanism may be considered for NW1, Mcol1C may fold according to the quasi-stochastic folding model involving disulfide bond reshuffling and conformational changes, locking the native disulfide conformations. The study further demonstrates the power of MD simulations to detect local structural preferences in rather dynamic systems such as the open, non-disulfide bonded forms of NW1 and Mcol1C, which complement published information from NMR backbone residual dipolar couplings. Because the backbone structural preferences encoded by the amino acid sequence embedding the cysteines influence which disulfide connectivities are formed, the data are generally interesting for a better understanding of oxidative folding and the design of disulfide stabilized therapeutics.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Gromos ; Nowa ; Cysteine-rich Domain ; Disulfide Bond Pattern ; Hydra ; Minicollagen-1 ; Molecular Dynamics Simulations ; Oxidative Folding; Gromos Force-field; Folding Pathways; Nematocyst Wall; Amino-acids; Protein; Peptides; Minicollagen; Domain; Hydra; Conformations
Sprache englisch
Veröffentlichungsjahr 2015
HGF-Berichtsjahr 2015
ISSN (print) / ISBN 1075-2617
e-ISSN 1099-1387
Zeitschrift Journal of Peptide Science
Quellenangaben Band: 21, Heft: 6, Seiten: 480-494 Artikelnummer: , Supplement: ,
Verlag Wiley
Verlagsort Hoboken
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Structural Biology (STB)
POF Topic(s) 30505 - New Technologies for Biomedical Discoveries
Forschungsfeld(er) Enabling and Novel Technologies
PSP-Element(e) G-503000-006
PubMed ID 25781269
DOI 10.1002/psc.2765
WOS ID WOS:000354732200006
Scopus ID 84929578182
Erfassungsdatum 2015-03-19
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