Deutsch
 
Hilfe Datenschutzhinweis Impressum
  DetailsucheBrowse

Datensatz

DATENSATZ AKTIONENEXPORT
  Human γS-Crystallin–Copper Binding Helps Buffer against Aggregation Caused by Oxidative Damage

Roskamp, K. W., Azim, S., Kassier, G., Norton-Baker, B., Sprague-Piercy, M. A., Miller, R. J. D., et al. (2020). Human γS-Crystallin–Copper Binding Helps Buffer against Aggregation Caused by Oxidative Damage. Biochemistry, 59(25), 2371-2385. doi:10.1021/acs.biochem.0c00293.

Item is

Basisdaten

einblenden: ausblenden:
Genre: Zeitschriftenartikel

Dateien

einblenden: Dateien
ausblenden: Dateien
:
acs.biochem.0c00293.pdf (Verlagsversion), 10MB
 
Datei-Permalink:
-
Name:
acs.biochem.0c00293.pdf
Beschreibung:
-
OA-Status:
Sichtbarkeit:
Privat
MIME-Typ / Prüfsumme:
application/pdf
Technische Metadaten:
Copyright Datum:
-
Copyright Info:
-
Lizenz:
-
:
bi0c00293_si_001.pdf (Ergänzendes Material), 101MB
Name:
bi0c00293_si_001.pdf
Beschreibung:
Supporting information: Additional TEM images and characterization data for the γS-crystallin aggregates; FTIR spectra, SEC and SDS–PAGE data, and mass spectrometry data; a figure showing potential ion-binding sites; and tables of literature data for the cysteine content of human crystallin proteins
OA-Status:
Keine Angabe
Sichtbarkeit:
Öffentlich
MIME-Typ / Prüfsumme:
application/pdf / [MD5]
Technische Metadaten:
Copyright Datum:
-
Copyright Info:
-
Lizenz:
-

Externe Referenzen

einblenden:
ausblenden:
externe Referenz:
https://dx.doi.org/10.1021/acs.biochem.0c00293 (Verlagsversion)
Beschreibung:
-
OA-Status:
Keine Angabe

Urheber

einblenden:
ausblenden:
 Urheber:
Roskamp, K. W.1, Autor
Azim, S.2, 3, Autor           
Kassier, G.2, 3, Autor           
Norton-Baker, B.1, 2, 3, Autor           
Sprague-Piercy, M. A.4, Autor
Miller, R. J. D.2, 3, 5, Autor           
Martin, R. W.1, 4, Autor
Affiliations:
1Department of Chemistry, University of California, ou_persistent22              
2Miller Group, Atomically Resolved Dynamics Department, Max Planck Institute for the Structure and Dynamics of Matter, Max Planck Society, ou_1938288              
3Center for Free Electron Laser Science, ou_persistent22              
4Department of Molecular Biology and Biochemistry, University of California, ou_persistent22              
5Departments of Chemistry and Physics, University of Toronto, ou_persistent22              

Inhalt

einblenden:
ausblenden:
Schlagwörter: -
 Zusammenfassung: Divalent metal cations can play a role in protein aggregation diseases, including cataract. Here we compare the aggregation of human γS-crystallin, a key structural protein of the eye lens, via mutagenesis, UV light damage, and the addition of metal ions. All three aggregation pathways result in globular, amorphous structures that do not elongate into fibers. We also investigate the molecular mechanism underlying copper (II)-induced aggregation. This work was motivated by the observation that zinc (II)-induced aggregation of γS-crystallin is driven by intermolecular bridging of solvent-accessible cysteine residues, while in contrast, copper (II)-induced aggregation of this protein is exacerbated by the removal of solvent-accessible cysteines via mutation. Here we find that copper (II)-induced aggregation results from a complex mechanism involving multiple interactions with the protein. The initial protein-metal interactions result in the reduction of Cu(II) to Cu(I) with concomitant oxidation of γS-crystallin. In addition to the intermolecular disulfides that represent a starting point for aggregation, intramolecular disulfides also occur the cysteine loop, a region of the N-terminal domain that was previously found to mediate the early stages of cataract formation. This previously unobserved ability of γS-crystallin to transfer disulfides intramolecularly suggests that it may serve as an oxidation sink for the lens after glutathione levels have become depleted during aging. γS-crystallin thus serves as the last line of defense against oxidation in the eye lens, a result that underscores the chemical functionality of this protein, which is generally considered to play a purely structural role.

Details

einblenden:
ausblenden:
Sprache(n): eng - English
 Datum: 2020-06-072020-04-102020-06-082020-06-30
 Publikationsstatus: Erschienen
 Seiten: 15
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: Expertenbegutachtung
 Identifikatoren: DOI: 10.1021/acs.biochem.0c00293
 Art des Abschluß: -

Veranstaltung

einblenden:

Entscheidung

einblenden:

Projektinformation

einblenden: ausblenden:
Projektname : The authors acknowledge Dmitry Fishman for assistance and management of optical instruments at the UCI Laser Spectroscopy Labs, Ben Katz and Felix Grun for extensive help with mass spectrometry data analysis and management of the UCI Mass Spectrometry Facility, Friedjof Tellkamp, Hendrik Schikora, and Martin Kollewe from the machine physics support group, and Djordje Gitaric and Josef Gonschior from the technical staff of the Max Planck Institute for the Structure and Dynamics of Matter for setting up the UVB source. This work builds on discussions at the 2018 Crystallin Satellite Biophysical Society Meeting in San Francisco, and we are grateful to the participants for ideas and suggestions.
Grant ID : -
Förderprogramm : -
Förderorganisation : -

Quelle 1

einblenden:
ausblenden:
Titel: Biochemistry
Genre der Quelle: Zeitschrift
 Urheber:
Affiliations:
Ort, Verlag, Ausgabe: Columbus, Ohio : American Chemical Society
Seiten: - Band / Heft: 59 (25) Artikelnummer: - Start- / Endseite: 2371 - 2385 Identifikator: ISSN: 0006-2960
CoNE: https://pure.mpg.de/cone/journals/resource/954925384103