Phospholipid-Cytochrome c Interaction

Tuominen, Esa K. J.; Wallace, Carmichael J. A.; Kinnunen, Paavo K.J.

doi:10.1074/jbc.m200056200

Cited by 294 publications

(125 citation statements)

References 38 publications

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“…It is noteworthy that the lipid chains of PI(4,5)P 2 extend in opposite directions, with the 1Ј-chain inserted into the lipid bilayer and the 2Ј-chain sequestered by the protein. This conformation, and the predicted membrane-binding mode, are strikingly similar to those predicted in ''extended lipid'' phospholipid-cytochrome c models (41)(42)(43) and could be used to anchor other proteins to membranes as well (44). Although extrusion of the 2Ј-chain from lamellar membranes might intuitively be considered energetically expensive, a number of studies suggest this can actually relieve conformational stress caused by lipids with propensities for negative membrane curvature (41).…”

Section: )mentioning

confidence: 81%

“…Although extrusion of the 2Ј-chain from lamellar membranes might intuitively be considered energetically expensive, a number of studies suggest this can actually relieve conformational stress caused by lipids with propensities for negative membrane curvature (41). Conformational dynamic studies also suggest that the 2Ј-chain is specifically favored for extrusion from the bilayer (44), and fluorescence quenching experiments indicate that the 2Ј-acyl chain of a brominated phospholipid is sequestered by cytochrome c upon binding to liposomes (43). Thus, the PI(4,5)P 2 -binding mode shown in Fig.…”

Section: )mentioning

confidence: 99%

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Structural basis for targeting HIV-1 Gag proteins to the plasma membrane for virus assembly

Saad

Miller

Tai

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

518

774

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During the late phase of HIV type 1 (HIV-1) replication, newly synthesized retroviral Gag proteins are targeted to the plasma membrane of most hematopoietic cell types, where they colocalize at lipid rafts and assemble into immature virions. Membrane binding is mediated by the matrix (MA) domain of Gag, a 132-residue polypeptide containing an N-terminal myristyl group that can adopt sequestered and exposed conformations. Although exposure is known to promote membrane binding, the mechanism by which Gag is targeted to specific membranes has yet to be established . Here we show that PI(4,5)P 2 binds directly to HIV-1 MA, inducing a conformational change that triggers myristate exposure. Related phosphatidylinositides PI, PI(3)P, PI(4)P, PI(5)P, and PI(3,5)P 2 do not bind MA with significant affinity or trigger myristate exposure. Structural studies reveal that PI(4,5)P 2 adopts an ''extended lipid'' conformation, in which the inositol head group and 2-fatty acid chain bind to a hydrophobic cleft, and the 1-fatty acid and exposed myristyl group bracket a conserved basic surface patch previously implicated in membrane binding. Our findings indicate that PI(4,5)P 2 acts as both a trigger of the myristyl switch and a membrane anchor and suggest a potential mechanism for targeting Gag to membrane rafts. matrix protein ͉ membrane targeting ͉ NMR ͉ lipid rafts

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Section: )mentioning

confidence: 81%

Section: )mentioning

confidence: 99%

Structural basis for targeting HIV-1 Gag proteins to the plasma membrane for virus assembly

Saad

Miller

Tai

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

518

774

View full text Add to dashboard Cite

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“…The relevant conformational changes and the partial unfolding occurring in cyt c when the protein binds to CL [18,28] may be reverted. We previously reported that ATP disrupts the oleic acid-cyt c interaction by binding to a specific site of the protein; thus the nucleotide regulates the cyt c conformational transitions [6,17].…”

Section: Induction and Inhibition Of Peroxidase Activitymentioning

confidence: 99%

“…4A). It is likely that ATP competes with the CL head groups for a binding site on cyt c that comprises basic residues, such as Lys88 and Arg91 previously proposed to form the ATP binding site [6,28]. Although ATP seems to behave as a regulator of the conformational transitions and of the peroxidase activity also in the case of H26Y mutant, in this case its effect results lower since the complete recovery of the properties typical of the unbound protein (as the integrity of Fe-S(Met80) bond and poor peroxidase activity) were not observed at the physiological cellular ATP concentration values tested here (1-10 mM) (Fig.…”

Section: Induction and Inhibition Of Peroxidase Activitymentioning

confidence: 99%

Conversion of cytochrome c into a peroxidase: Inhibitory mechanisms and implication for neurodegenerative diseases

Patriarca

Polticelli

Piro

et al. 2012

Archives of Biochemistry and Biophysics

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a b s t r a c tA further function of cytochrome c (cyt c), beyond respiration, is realized outside mitochondria in the apoptotic program. In the early events of apoptosis, the interaction of cyt c with a mitochondrion-specific phospholipid, cardiolipin (CL), brings about a conformational transition of the protein and acquirement of peroxidase activity. The hallmark of cyt c with peroxidase activity is its partial unfolding accompanied by loosening of the Fe sixth axial bond and an enhanced access of the heme catalytic site to small molecules like H 2 O 2 . To investigate the peroxidase activity of non-native cyt c, different forms of the protein were analyzed with the aim to correlate their structural features with the acquired enzymatic activity and apoptogenic properties (wt cyt c/CL complex and two single cyt c variants, H26Y and Y67H, free and bound to CL). The results suggest that cyt c may respond to different environments by changing its fold thus favouring the exertion of different biological functions in different pathophysiological cell conditions. Transitions among different conformations are regulated by endogenous molecules such as ATP and may be affected by synthetic molecules such as minocycline, thus suggesting a mechanism explaining its use as therapeutic agent impacting on disease-associated oxidative and apoptotic mechanisms.

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“…Ionic strength modulates the cyt c/CL interaction around neutrality; the cyt c/CL complex spontaneously forms at low ionic strength but tends to dissociate as the ionic strength increases [5,6]. The "extended lipid conformation" model [24,25] hypothesizes that at the C-site one acyl chain of CL accommodates into the protein interior by extending from the surface to the heme pocket region through a hydrophobic channel close to the small helix comprising the invariant residue Asn52. Conversely, the other chain of CL points in the opposite direction from the head group.…”

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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Phospholipid-Cytochrome c Interaction

Cited by 294 publications

References 38 publications

Structural basis for targeting HIV-1 Gag proteins to the plasma membrane for virus assembly

Structural basis for targeting HIV-1 Gag proteins to the plasma membrane for virus assembly

Conversion of cytochrome c into a peroxidase: Inhibitory mechanisms and implication for neurodegenerative diseases

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

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