Reinwarth, Michael ; Avrutina, Olga ; Fabritz, Sebastian ; Kolmar, Harald (2014)
Fragmentation follows structure: top-down mass spectrometry elucidates the topology of engineered cystine-knot miniproteins.
In: PLOS ONE, 9 (10)
doi: 10.1371/journal.pone.0108626
Artikel, Bibliographie
Dies ist die neueste Version dieses Eintrags.
Kurzbeschreibung (Abstract)
Over the last decades the field of pharmaceutically relevant peptides has enormously expanded. Among them, several peptide families exist that contain three or more disulfide bonds. In this context, elucidation of the disulfide patterns is extremely important as these motifs are often prerequisites for folding, stability, and activity. An example of this structure-determining pattern is a cystine knot which comprises three constrained disulfide bonds and represents a core element in a vast number of mechanically interlocked peptidic structures possessing different biological activities. Herein, we present our studies on disulfide pattern determination and structure elucidation of cystine-knot miniproteins derived from Momordica cochinchinensis peptide MCoTI-II, which act as potent inhibitors of human matriptase-1. A top-down mass spectrometric analysis of the oxidised and bioactive peptides is described. Following the detailed sequencing of the peptide backbone, interpretation of the MS³ spectra allowed for the verification of the knotted topology of the examined miniproteins. Moreover, we found that the fragmentation pattern depends on the knottin’s folding state, hence, tertiary structure, which to our knowledge has not been described for a top-down MS approach before.
| Typ des Eintrags: | Artikel |
|---|---|
| Erschienen: | 2014 |
| Autor(en): | Reinwarth, Michael ; Avrutina, Olga ; Fabritz, Sebastian ; Kolmar, Harald |
| Art des Eintrags: | Bibliographie |
| Titel: | Fragmentation follows structure: top-down mass spectrometry elucidates the topology of engineered cystine-knot miniproteins |
| Sprache: | Englisch |
| Publikationsjahr: | 2014 |
| Ort: | San Francisco, California, US |
| Verlag: | PLOS |
| Titel der Zeitschrift, Zeitung oder Schriftenreihe: | PLOS ONE |
| Jahrgang/Volume einer Zeitschrift: | 9 |
| (Heft-)Nummer: | 10 |
| Kollation: | 10 Seiten |
| DOI: | 10.1371/journal.pone.0108626 |
| Zugehörige Links: | |
| Kurzbeschreibung (Abstract): | Over the last decades the field of pharmaceutically relevant peptides has enormously expanded. Among them, several peptide families exist that contain three or more disulfide bonds. In this context, elucidation of the disulfide patterns is extremely important as these motifs are often prerequisites for folding, stability, and activity. An example of this structure-determining pattern is a cystine knot which comprises three constrained disulfide bonds and represents a core element in a vast number of mechanically interlocked peptidic structures possessing different biological activities. Herein, we present our studies on disulfide pattern determination and structure elucidation of cystine-knot miniproteins derived from Momordica cochinchinensis peptide MCoTI-II, which act as potent inhibitors of human matriptase-1. A top-down mass spectrometric analysis of the oxidised and bioactive peptides is described. Following the detailed sequencing of the peptide backbone, interpretation of the MS³ spectra allowed for the verification of the knotted topology of the examined miniproteins. Moreover, we found that the fragmentation pattern depends on the knottin’s folding state, hence, tertiary structure, which to our knowledge has not been described for a top-down MS approach before. |
| Freie Schlagworte: | Arginine, Disulfide bonds, Signal peptides, Cysteine, Amino acid analysis, Proteases, Protein structure, Ionization |
| Sachgruppe der Dewey Dezimalklassifikatin (DDC): | 500 Naturwissenschaften und Mathematik > 540 Chemie 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie |
| Fachbereich(e)/-gebiet(e): | 07 Fachbereich Chemie 07 Fachbereich Chemie > Clemens-Schöpf-Institut > Fachgebiet Biochemie 07 Fachbereich Chemie > Clemens-Schöpf-Institut |
| Hinterlegungsdatum: | 21 Aug 2024 05:19 |
| Letzte Änderung: | 21 Aug 2024 05:19 |
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| Suche nach Titel in: | TUfind oder in Google |
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Fragmentation follows structure: top-down mass spectrometry elucidates the topology of engineered cystine-knot miniproteins. (deposited 20 Aug 2024 13:25)
- Fragmentation follows structure: top-down mass spectrometry elucidates the topology of engineered cystine-knot miniproteins. (deposited 21 Aug 2024 05:19) [Gegenwärtig angezeigt]
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