Journal
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
Volume 134, Issue 45, Pages 18713-18723Publisher
AMER CHEMICAL SOC
DOI: 10.1021/ja307426k
Keywords
-
Categories
Funding
- NIH [RO1-GM098502]
- Direct For Biological Sciences
- Div Of Biological Infrastructure [1039423] Funding Source: National Science Foundation
Ask authors/readers for more resources
Interactions of cytochrome c (cyt c) with cardiolipin (CL) partially Unfold the protein, activating its peroxidase function, a critical. event, in the. execution of apoptosis, However, structutal. features of the altered protein species in:the:heterogeneous ensemble are difficult to probe with ensemble averaging. Analyses of the dye-to-heme distance distributions P(r) from time resolved FRET (TR-FRET) have uncovered two, distinct types of CL bound cyt c confoimations; extended and compact We have combined TR-FRET, fluorescence correlation spectroscopy (FCS), and biolayer interferometry to develop a systematic Understanding of the functional partitioning between the two conformations. The two subpopulations are in equilibrium with each other, with a submillisecond rate of conformational exchange reflecting the protein folding into a compact non-native state, as well as protein interactions with the lipid surface. Electrostatic interactions with the negatively charged lipid surface that correlate with physiologically relevant changes in CL concentrations strongly affect the kinetics of cyt c binding and conformational exchange. A predominantly peripheral binding mechanism, rather than deep protein insertion into the membrane, provides a rationale for the general denaturing effect of the CL surface and the large-scale protein unfolding. These findings closely relate to cyt c folding dynamics and suggest a general strategy for extending the time window in monitoring the kinetics of folding
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available