Projects per year
Abstract
Thrombocytopenia 4 is an inherited autosomal dominant thrombocytopenia, which occurs due to mutations in the human gene for cytochrome c that results in enhanced mitochondrial apoptotic activity. The Gly41Ser mutation was the first to be reported. Here we report stopped-flow kinetic studies of azide binding to human ferricytochrome c and its Gly41Ser variant, together with backbone amide H/D exchange and 15N-relaxation dynamics using NMR spectroscopy, to show that alternative conformations are kinetically and thermodynamically more readily accessible for the Gly41Ser variant than for the wild-type protein. Our work reveals a direct conformational link between the 40-57 Ω-loop in which residue 41 resides and the dynamical properties of the axial ligand to the heme iron, Met80, such that the replacement of glycine by serine promotes the dissociation of the Met80 ligand, thereby increasing the population of a peroxidase active state, which is a key non-native conformational state in apoptosis.
Original language | English |
---|---|
Article number | 30447 |
Journal | Scientific Reports |
Volume | 6 |
DOIs | |
Publication status | Published - 27 Jul 2016 |
Profiles
-
Tharin Blumenschein
- School of Chemistry, Pharmacy and Pharmacology - Associate Professor in Biomolecular NMR Spectroscopy
- Centre for Molecular and Structural Biochemistry - Member
- Chemistry of Life Processes - Member
Person: Research Group Member, Research Centre Member, Academic, Teaching & Research
Projects
- 2 Finished
-
-
Fat(al) attraction of cytochrome c: A new approach to study protein-lipid interactions
1/02/14 → 31/01/17
Project: Research
Research output
- 49 Citations (Scopus)
- 1 Article
-
Backbone resonance assignments of ferric human cytochrome c and the pro-apoptotic G41S mutant in the ferric and ferrous states
Karsisiotis, A. I., Deacon, O. M., Rajagopal, B. S., Macdonald, C., Blumenschein, T. M. A., Moore, G. & Worrall, J. A. R., Oct 2015, In: Biomolecular NMR Assignments. 9, 2, p. 415-419 5 p.Research output: Contribution to journal › Article › peer-review
Open AccessFile6 Citations (Scopus)16 Downloads (Pure)