Subtle Change in the Charge Distribution of Surface Residues May Affect the Secondary Functions of Cytochrome c
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
View Archive Info| Field | Value | |
| Title |
Subtle Change in the Charge Distribution of Surface Residues
May Affect the Secondary Functions of Cytochrome c
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| Creator |
Paul, Simanta Sarani
Sil, Pallabi Haldar, Shubhasis Mitra, Samaresh Chattopadhyay, Krishnananda |
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| Subject |
Structural Biology & Bioinformatics
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| Description |
Although the primary function of cytochrome c (cyt c) is electron
transfer, the protein caries out an additional secondary
function involving its interaction with membrane cardiolipin
(CDL), its peroxidase activity, and the initiation of apoptosis.
Whereas the primary function of cyt c is essentially conserved,
its secondary function varies depending on the source of the
protein. We report here a detailed experimental and computational
study, which aims to understand, at the molecular level,
the difference in the secondary functions of cyt c obtained from
horse heart (mammalian) and Saccharomyces cerevisiae (yeast).
The conformational landscape of cyt c has been found to be heterogeneous,
consisting of an equilibrium between the compact
and extended conformers as well as the oligomeric species.
Because the determination of relative populations of these conformers
is difficult to obtain by ensemble measurements, we
used fluorescence correlation spectroscopy (FCS), a method
that offers single-molecule resolution. The population of different
species is found to depend on multiple factors, including the
protein source, the presence of CDL and urea, and their concentrations.
The complex interplay between the conformational
distribution and oligomerization plays a crucial role in the variation
of the pre-apoptotic regulation of cyt c observed from different
sources. Finally, computational studies reveal that the
variation in the charge distribution at the surface and the charge
reversal sites may be the key determinant of the conformational
stability of cyt c.
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| Publisher |
American Society for Biochemistry and Molecular Biology
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| Date |
2015
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| Type |
Article
PeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://www.eprints.iicb.res.in/2221/1/JOURNAL_OF_BIOLOGICAL_CHEMISTRY__V._290__(_23)_._14476%2D14490;2015[6].pdf
Paul, Simanta Sarani and Sil, Pallabi and Haldar, Shubhasis and Mitra, Samaresh and Chattopadhyay, Krishnananda (2015) Subtle Change in the Charge Distribution of Surface Residues May Affect the Secondary Functions of Cytochrome c. The Journal of Biological Chemistry, 290 (23). pp. 14476-14490. |
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| Relation |
http://dx.doi.org/10.1074/jbc.M114.607010
http://www.eprints.iicb.res.in/2221/ |
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