The effects of ATP and sodium chloride on the cytochrome c–cardiolipin interaction: The contrasting behavior of the horse heart and yeast proteins

Sinibaldi, Federica; Droghetti, Enrica; Polticelli, Fabio; Piro, María Cristina; Pierro, Donato Di; Ferri, Tommaso; Smulevich, Giulietta; Santucci, Roberto

doi:10.1016/j.jinorgbio.2011.07.022

Cited by 28 publications

(40 citation statements)

References 42 publications

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“…Conversely, in accord with the CD data, significant changes are observed in the corresponding spectra of the Lys73Asn and Lys72/73Asn mutants (Figures 6 and 7). The CL-induced changes in the case of the Lys73Asn mutant, although similar to those noted for the wt protein in the presence of CL where a misligated Lys−Fe−His low-spin species is formed upon CL complexation, 28 are more pronounced, indicating a more extensive conversion to the misligated Lys−Fe−His species. The RR spectra show progressive variations, particularly an increase in the relative intensity of the band at 412 cm −1 and a frequency downshift of the ν 8 mode at 348 cm −1 , upon increasing the CL concentration until a CL:cyt c molar ratio of 5 is reached.…”

Section: Biochemistrysupporting

confidence: 66%

Role of Lysines in Cytochrome c–Cardiolipin Interaction

et al. 2013

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Cytochrome c undergoes structural variations during the apoptotic process; such changes have been related to modifications occurring in the protein when it forms a complex with cardiolipin, one of the phospholipids constituting the mitochondrial membrane. Although several studies have been performed to identify the site(s) of the protein involved in the cytochrome c−cardiolipin interaction, to date the location of this hosting region(s) remains unidentified and is a matter of debate. To gain deeper insight into the reaction mechanism, we investigate the role that the Lys72, Lys73, and Lys79 residues play in the cytochrome c−cardiolipin interaction, as these side chains appear to be critical for cytochrome c−cardiolipin recognition. The Lys72Asn, Lys73Asn, Lys79Asn, Lys72/73Asn, and Lys72/73/79Asn mutants of horse heart cytochrome c were produced and characterized by circular dichroism, ultraviolet−visible, and resonance Raman spectroscopies, and the effects of the mutations on the interaction of the variants with cardiolipin have been investigated. The mutants are characterized by a subpopulation with non-native axial coordination and are less stable than the wild-type protein. Furthermore, the mutants lacking Lys72 and/or Lys79 do not bind cardiolipin, and those lacking Lys73, although they form a complex with the phospholipid, do not show any peroxidase activity. These observations indicate that the Lys72, Lys73, and Lys79 residues stabilize the native axial Met80−Fe(III) coordination as well as the tertiary structure of cytochrome c. Moreover, while Lys72 and Lys79 are critical for cytochrome c−cardiolipin recognition, the simultaneous presence of Lys72, Lys73, and Lys79 is necessary for the peroxidase activity of cardiolipin-bound cytochrome c.

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Section: Biochemistrysupporting

confidence: 66%

Role of Lysines in Cytochrome c–Cardiolipin Interaction

et al. 2013

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“…The interaction between cyt c and CDL has been studied and reviewed extensively in the (5,30,38,60,61). The data presented here are described schematically in Fig.…”

Section: Discussionmentioning

confidence: 99%

“…After vigorous stirring and 10 freeze and thaw cycles, the liposome suspension was extruded 31 times using polycarbonate membranes with 100-nm pore size (38).…”

Section: Methodsmentioning

confidence: 99%

Subtle Change in the Charge Distribution of Surface Residues May Affect the Secondary Functions of Cytochrome c

Paul¹,

Sil²,

Haldar³

et al. 2015

Journal of Biological Chemistry

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Background:The cardiolipin (CDL) binding and the peroxidase activity of cytochrome c (cyt c) vary with the protein source. Results: The CDL binding and the peroxidase activity of cyt c depend on conformational heterogeneity and oligomerization. Conclusion: Subtle variations in the surface residues of cyt c influence its conformational dynamics and stability. Significance: Secondary functions of cyt c have been studied at single-molecule resolution.

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“…In contrast to the previous investigation, where a positively charged residue was replaced by a polar side chain carrying no net charge (Lys → Asn mutation), in the present study the Lys residues have been replaced by Arg carrying a positive charge at neutral pH as Lys, but with a different structure, and the non-polar, aliphatic amino acid, Ala. The present study has been performed on ferric horse heart cyt c, which behaves similar to the human counterpart [29] and actively participates in cell apoptosis [4,[30][31][32][33].…”

Section: Introductionmentioning

confidence: 99%

The key role played by charge in the interaction of cytochrome c with cardiolipin

et al. 2016

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mutations cancel the CL-dependent peroxidase activity of cyt c; furthermore, CL does not interact with the Lys72Asn mutant. In the present paper, we extend our study to the Lys → Arg mutants to investigate the influence exerted by the charge possessed by the residues located at positions 72 and 73 on the cyt c/CL interaction. On the basis of the present work a number of overall conclusions can be drawn: (i) position 72 must be occupied by a positively charged residue to assure cyt c/CL recognition; (ii) the Arg residues located at positions 72 and 73 permit cyt c to react with CL; (iii) the replacement of Lys72 with Arg weakens the second (low-affinity) binding transition; (iv) the Lys73Arg mutation strongly increases the peroxidase activity of the CL-bound protein.Abstract Cytochrome c undergoes structural variations upon binding of cardiolipin, one of the phospholipids constituting the mitochondrial membrane. Although several mechanisms governing cytochrome c/cardiolipin (cyt c/CL) recognition have been proposed, the interpretation of the process remains, at least in part, unknown. To better define the steps characterizing the cyt c-CL interaction, the role of Lys72 and Lys73, two residues thought to be important in the protein/lipid binding interaction, were recently investigated by mutagenesis. The substitution of the two (positively charged) Lys residues with Asn revealed that such Electronic supplementary material The online version of this article

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The effects of ATP and sodium chloride on the cytochrome c–cardiolipin interaction: The contrasting behavior of the horse heart and yeast proteins

Cited by 28 publications

References 42 publications

Role of Lysines in Cytochrome c–Cardiolipin Interaction

Role of Lysines in Cytochrome c–Cardiolipin Interaction

Subtle Change in the Charge Distribution of Surface Residues May Affect the Secondary Functions of Cytochrome c

The key role played by charge in the interaction of cytochrome c with cardiolipin

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