@article{76d3ff9641644a5cb402da1b9aac5423,
title = "Surface-Binding to Cardiolipin Nanodomains Triggers Cytochrome c Pro-apoptotic Peroxidase Activity via Localized Dynamics",
abstract = "The peroxidation of cardiolipins by reactive oxygen species, which is regulated and enhanced by cytochrome c (cyt c), is a critical signaling event in mitochondrial apoptosis. We probe the molecular underpinnings of this mitochondrial death signal through structural and functional studies of horse heart cyt c binding to mixed-lipid membranes containing cardiolipin with mono- and polyunsaturated acyl chains. Lipidomics reveal the selective oxidation of polyunsaturated fatty acid (PUFA) cardiolipin (CL), while multidimensional solid-state NMR probes the structure and dynamics of the membrane and the peripherally bound protein. The hydrophilic milieu at the membrane interface stabilizes a native-like fold, but also leads to localized flexibility at the membrane-interacting protein face. PUFA CL acts as both a preferred substrate and a dynamic regulator by affecting the dynamics of the cyt c N70-I85 Ω loop, which covers the heme cavity.",
keywords = "cytochrome, cardiolipin, mitochondrial protein, apoptosis, membrane protein, PUFA, protein structure and dynamics, membrane oxidation, lipidomics, solid-state NMR, FERRICYTOCHROME-C, NATIVE-LIKE, NMR, MITOCHONDRIA, MEMBRANES, PROTEINS, TRANSITIONS, COEXISTENCE, INHIBITORS, RESOLUTION",
author = "Mingyue Li and Abhishek Mandal and Tyurin, \{Vladimir A.\} and Maria DeLucia and Jinwoo Ahn and Kagan, \{Valerian E.\} and \{van der Wel\}, \{Patrick C. A.\}",
year = "2019",
month = may,
day = "7",
doi = "10.1016/j.str.2019.02.007",
language = "English",
volume = "27",
pages = "806--815.e4",
journal = "Structure",
issn = "0969-2126",
publisher = "Cell Press",
number = "5",
}