Backbone resonance assignments of ferric human cytochrome c and the pro-apoptotic G41S mutant in the ferric and ferrous states

Karsisiotis, Andreas Ioannis, Deacon, Oliver M., Rajagopal, Badri S., Macdonald, Colin, Blumenschein, Tharin M. A. ORCID:, Moore, Geoff and Worrall, Jonathan A. R. (2015) Backbone resonance assignments of ferric human cytochrome c and the pro-apoptotic G41S mutant in the ferric and ferrous states. Biomolecular NMR Assignments, 9 (2). pp. 415-419. ISSN 1874-2718

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Human cytochrome c is a multi-functional protein with key roles in both the mitochondrial electron transfer chain and in apoptosis. In the latter, a complex formed between the mitochondrial phospholipid cardiolipin and cytochrome c is crucial for instigating the release of pro-apoptotic factors, including cytochrome c, from the mitochondrion into the cytosol. The G41S mutant of human cytochrome c is the only known disease-related variant of cytochrome c and causes increased apoptotic activity in patients with autosomal dominant thrombocytopenia. NMR spectroscopy can be used to investigate the interaction of human cytochrome c with cardiolipin and the structural and dynamic factors, which may contribute to enhanced apoptotic activity for the G41S mutant. We present here essentially full backbone amide resonance assignments for ferric human cytochrome c (98 %) as well as assignments of both the ferric (92 %) and ferrous (95 %) forms of the G41S mutant. Backbone amide chemical shift differences between the wild type and G41S mutant in the ferric state reveals significant changes around the mutation site, with many other amides also affected. This suggests the possibility of increased dynamics and/or a change in the paramagnetic susceptibility tensor of the G41S mutant relative to the wild type protein.

Item Type: Article
Uncontrolled Keywords: human cytochrome c,mitochondria,apoptosis,paramagnetic nmr,sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School: Faculty of Science
Faculty of Science > School of Chemistry
UEA Research Groups: Faculty of Science > Research Groups > Biophysical Chemistry (former - to 2017)
Faculty of Science > Research Groups > Chemistry of Life Processes
Faculty of Science > Research Centres > Centre for Molecular and Structural Biochemistry
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Depositing User: Pure Connector
Date Deposited: 23 Oct 2015 15:01
Last Modified: 21 Oct 2022 01:03
DOI: 10.1007/s12104-015-9621-3

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