Functional binding of cardiolipin to cytochromec oxidase

Robinson, N.

doi:10.1007/bf00762857

Cited by 246 publications

(167 citation statements)

References 63 publications

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“…Interestingly, the two high-affinity CL binding sites were located in close proximity to the proton channels and were associated with the regulation of the enzyme (32,33), whereas the low-affinity binding sites were linked to stabilization of subunits VIa and VIb, important for dimerization of CcO (30,34). A loss of CcO function in the absence of CL was shown recently through destabilization of quaternary structure following CL removal (13,14).…”

Section: Discussionmentioning

confidence: 97%

Dimer interface of bovine cytochrome c oxidase is influenced by local posttranslational modifications and lipid binding

Liko

Degiacomi

Mohammed

et al. 2016

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

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Bovine cytochrome c oxidase is an integral membrane protein complex comprising 13 protein subunits and associated lipids. Dimerization of the complex has been proposed; however, definitive evidence for the dimer is lacking. We used advanced mass spectrometry methods to investigate the oligomeric state of cytochrome c oxidase and the potential role of lipids and posttranslational modifications in its subunit interfaces. Mass spectrometry of the intact protein complex revealed that both the monomer and the dimer are stabilized by large lipid entities. We identified these lipid species from the purified protein complex, thus implying that they interact specifically with the enzyme. We further identified phosphorylation and acetylation sites of cytochrome c oxidase, located in the peripheral subunits and in the dimer interface, respectively. Comparing our phosphorylation and acetylation sites with those found in previous studies of bovine, mouse, rat, and human cytochrome c oxidase, we found that whereas some acetylation sites within the dimer interface are conserved, suggesting a role for regulation and stabilization of the dimer, phosphorylation sites were less conserved and more transient. Our results therefore provide insights into the locations and interactions of lipids with acetylated residues within the dimer interface of this enzyme, and thereby contribute to a better understanding of its structure in the natural membrane. Moreover dimeric cytochrome c oxidase, comprising 20 transmembrane, six extramembrane subunits, and associated lipids, represents the largest integral membrane protein complex that has been transferred via electrospray intact into the gas phase of a mass spectrometer, representing a significant technological advance.cytochrome c oxidase | mass spectrometry | lipids

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Section: Discussionmentioning

confidence: 97%

Dimer interface of bovine cytochrome c oxidase is influenced by local posttranslational modifications and lipid binding

Liko

Degiacomi

Mohammed

et al. 2016

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

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“…The position of the aryl azide attachment to CL is not critical for its binding to CcO. Long chain fatty acids or large fluorescent groups linked to the 2′-hydroxyl of the bridge glycerol or arylazido groups placed at the end of one of the acyl groups do not alter CL binding to CcO (5).…”

Section: Discussionmentioning

confidence: 98%

Photolabeling of Cardiolipin Binding Subunits within Bovine Heart CytochromecOxidase

et al. 2005

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Subunits located near the cardiolipin binding sites of bovine heart cytochrome c oxidase (CcO) were identified by photolabeling with arylazido-cardiolipin analogues and detecting labeled subunits by reversed-phase HPLC and HPLC-electrospray ionization mass spectrometry. Two arylazidocontaining cardiolipin analogues were synthesized: (1) 2-SAND-gly-CL with a nitrophenylazido group attached to the polar headgroup of cardiolipin (CL) via a linker containing a cleavable disulfide; (2) 2′,2″-bis-(AzC 12 )-CL with two of the four fatty acid tails of cardiolipin replaced by 12-(N-4-azido-2-nitrophenyl) aminododecanoic acid. Both arylazido-CL derivatives were used to map the cardiolipin binding sites within two types of detergent-solubilized CcO: (1) intact 13-subunit CLcontaining CcO (three to four molecules of endogenous CL remain bound per CcO monomer); (2) 11-subunit CL-free CcO (subunits VIa and VIb are missing because they dissociate during CL removal). Upon the basis of these photolabeling studies, we conclude that (1) subunits VIIa, VIIc, and possibly VIII are located near the two high-affinity cardiolipin binding sites, which are present in either form of CcO, and (2) subunit VIa is located adjacent to the lower affinity cardiolipin binding site, which is only present in the 13-subunit form of CcO. These data are consistent with the recent CcO crystal structure in which one cardiolipin is located near subunit VIIa and a second is located near subunit VIa (PDB ID code 1V54 referenced in Tomitake, T. et al. (2003) Proc. Natl. Acad. Sci. U.S.A. 100, 15304−15309). However, we propose that a third cardiolipin is bound between subunits VIIa and VIIc near the entrance to the D-channel. Cardiolipin bound at this location could potentially function as a proton antenna to facilitate proton entry into the D-channel. If true, it would explain the CcO requirement of bound cardiolipin for full electron transport activity.Cardiolipin (diphosphatidylglycerol, CL 1 ) is a unique phospholipid found in membranes that couple electron transport to oxidative phosphorylation, for example, mitochondrial inner membrane and bacterial cytoplasmic membrane (2-4). In eukaryotes, CL is synthesized exclusively within the mitochondrion and is found only in the mitochondrial inner membrane. The structure of CL is quite different from other phospholipids. It contains three glycerols, two

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“…It has been known for long that it is associated with mitochondria and, more specifically, with proteins driving oxidative phosphorylation. 1,2 CL has been shown to copurify with different mitochondrial proteins like cytochrome c oxidase, 3,4 the adenine nucleotides carrier, 5,6 the F 0 F 1 -ATP synthase, 7,8 the orthophosphate carrier 9 and the bc 1 complex. 4 For most of them, CL has also been shown to be required for their optimal function.…”

Section: Introductionmentioning

confidence: 99%

“…1,2 CL has been shown to copurify with different mitochondrial proteins like cytochrome c oxidase, 3,4 the adenine nucleotides carrier, 5,6 the F 0 F 1 -ATP synthase, 7,8 the orthophosphate carrier 9 and the bc 1 complex. 4 For most of them, CL has also been shown to be required for their optimal function. For example, strong evidences suggest that CL participates in the interaction of cytochrome c with the outer face of the inner mitochondrial membrane, thereby ensuring the presence of a pool with limited solubility close to respiratory complexes III and IV, increasing the efficiency of electron transport.…”

Section: Introductionmentioning

confidence: 99%

Role of cardiolipin on tBid and tBid/Bax synergistic effects on yeast mitochondria

Gonzalvez

Rocchiccioli

et al. 2005

Cell Death Differ

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Functional binding of cardiolipin to cytochromec oxidase

Cited by 246 publications

References 63 publications

Dimer interface of bovine cytochrome c oxidase is influenced by local posttranslational modifications and lipid binding

Dimer interface of bovine cytochrome c oxidase is influenced by local posttranslational modifications and lipid binding

Photolabeling of Cardiolipin Binding Subunits within Bovine Heart CytochromecOxidase

Role of cardiolipin on tBid and tBid/Bax synergistic effects on yeast mitochondria

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