Cardiolipin modulates the secondary structure of the presequence peptide of cytochrome oxidase subunit IV: a 2D <sup>1</sup>H‐NMR study

Chupin, Vladimir; Leenhouts, Johanna M.; Kroon, Anton I.P.M. de; Kruijff, Ben de

doi:10.1016/0014-5793(95)01054-i

Cited by 27 publications

(20 citation statements)

References 42 publications

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“…The ADP/ATP carrier has an absolute requirement for CL to mediate nucleotide translocation (47). CL also modulates the secondary structure of cytochrome oxidase (48) and the activity of cytochrome C oxidase (49). The latter enzyme was stimulated by exogenous CL but not other phospholipids, a result similar to our present finding with streptococcal HAS.…”

Section: Discussionsupporting

confidence: 81%

The Active Streptococcal Hyaluronan Synthases (HASs) Contain a Single HAS Monomer and Multiple Cardiolipin Molecules

Tlapak-Simmons¹,

Kempner²,

Baggenstoss³

et al. 1998

Journal of Biological Chemistry

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The functional sizes of the two streptococcal hyaluronan synthases (HASs) were determined by radiation inactivation analysis of isolated membranes. The native enzymes in membranes from Group A Streptococcus pyogenes HAS and Group C Streptococcus equisimilis HAS were compared with the recombinant proteins expressed in Escherichia coli membranes. Based on their amino acid sequences, the masses of these four proteins as monomers are ϳ48 kDa. In all cases, loss of enzyme activity was a simple single exponential function with increasing radiation dose. The functional sizes calculated from these data were identical for the four HASs at ϳ64 kDa. In contrast, the sizes of the proteins estimated by the loss of antibody reactivity on Western blots were essentially identical at 41 kDa for the four HAS species, consistently lower than the functional size by ϳ23 kDa. Matrix-assisted laser desorption time of flight mass spectrometry analysis of purified S. pyogenes HAS-H 6 and S. equisimilis HAS-H 6 gave masses that differed by <0.07% from the predicted monomer sizes, which confirms that neither protein is posttranslationally modified or covalently attached to another protein. Ongoing studies indicate that the purified HAS enzymes require cardiolipin (CL) for maximal activity and stability. When irradiated membranes were detergent solubilized and the extracts were incubated with exogenous CL, the residual level of HAS activity increased. Consequently, the calculated functional size decreased by ϳ23 kDa to the expected size of the HAS monomer. The ϳ23-kDa larger size of the functional HAS enzyme, compared with the HAS monomer, is due, therefore, to CL molecules. We propose that the active streptococcal HA synthases are monomers in complex with ϳ16 CL molecules.

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Section: Discussionsupporting

confidence: 81%

The Active Streptococcal Hyaluronan Synthases (HASs) Contain a Single HAS Monomer and Multiple Cardiolipin Molecules

Tlapak-Simmons¹,

Kempner²,

Baggenstoss³

et al. 1998

Journal of Biological Chemistry

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“…In the presence of micelles of phospholipid analogs, the presequence of the subunit IV of the cytochrome oxidase (p25) has an amphiphilic structure at its N-terminus followed by a less structured C-terminal region [58]. Upon addition of cardiolipin (an anionic phospholipid) or in a negatively charged membrane mimetic environment, the micellebound p25 contains two helices separated by a proline residue at position 13 [59,60]. The mitochondrial presequence derived from the F~-ATPase fi-subunit also has two helical domains, the N-terminal helix being somewhat more stable [61].…”

Section: Specificity Of Mppmentioning

confidence: 99%

The mitochondrial processing peptidase: Function and specificity

Luciano

Géli

1996

Experientia

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Targeting signals of mitochondrial precursors are cleaved in the matrix during or after import by the mitochondrial processing peptidase (MPP). This enzyme consists of two nonidentical alpha- and beta-subunits each of molecular weight of about 50 kDa. In mammals and fungi, MPP is soluble in the matrix, whereas in plants the enzyme is part of the cytochrome bc1 complex. MPP is a metalloendopeptidase which has been classified as a member of the pitrilysin family on the basis of the HXXEHX76E zinc-binding motif present in beta-MPP. Both subunits of MPP are required for processing activity. The alpha-subunit of MPP, which probably recognizes a three-dimensional motif adopted by the presequence, presents the presequence to beta-MPP, which carries the catalytic active site. MPP acts as an endoprotease on chemically synthesized peptides corresponding to mitochondrial presequences. Matrix-targeting signals and MPP cleavage signals seem to be distinct, although the two signals may overlap within a given presequence. The structural element helix-turn-helix, that cleavable presequences adopt in a membrane mimetic environment, may be required for processing but is not sufficient for proteolysis. Binding of the presequence by alpha-MPP tolerates a high degree of mutations of the presequence. alpha-MPP may present a degenerated cleavage site motif to beta-MPP in an accessible conformation for processing. The conformation of mitochondrial presequences bound to MPP remains largely unknown.

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“…This function is inhibited by adriamycin, an antibiotic that specifically binds anionic phospholipids (12). The 25 amino acid presequence of cytochrome c oxidase (Cox) subunit IV (Cox4p), widely utilized as a model peptide for mitochondrial targeting sequences, is both stabilized and properly oriented by CL (13). Another unique property of CL is its ability to adopt non-bilayer structures in the presence of divalent cations such as calcium (14,15) which is a known regulator of mitochondrial function.…”

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confidence: 99%

Lack of Mitochondrial Anionic Phospholipids Causes an Inhibition of Translation of Protein Components of the Electron Transport Chain

Ostrander¹,

Zhang

Mileykovskaya

et al. 2001

Journal of Biological Chemistry

173

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Reduction of mitochondrial cardiolipin (CL) levels has been postulated to compromise directly the function of several essential enzymes and processes of the mitochondria. There is limited genetic evidence for the critical roles with which CL and its precursor phosphatidylglycerol (PG) have been associated. A null allele of the PGS1 gene from Saccharomyces cerevisiae, which encodes the enzyme responsible for the synthesis of the CL precursor PG phosphate, was created in a yeast strain in which PGS1 expression is exogenously regulated by doxycycline. The addition of increasing concentrations of doxycycline to the growth medium causes a proportional decrease to undetectable levels of PGS1 transcript, PG phosphate synthase activity, and PG plus CL. The doubling time of this strain with increasing doxycycline increases to senescence in non-fermentable carbon sources or at high temperatures, conditions that do not support growth of the pgs1⌬ strain. Doxycycline addition also causes mitochondrial abnormalities as observed by fluorescence microscopy. Products of four mitochondrial encoded genes (COX1, COX2, COX3, and COB) and one nuclear encoded gene (COX4) associated with the mitochondrial inner membrane are not present when PGS1 expression is fully repressed. No translation of these proteins can be detected in cells lacking the PGS1 gene product, although transcription and splicing appear unaffected. Protein import of other nuclear encoded proteins remains unaffected. The remaining proteins encoded by mitochondrial DNA are expressed and translated normally. Thus, the molecular basis for the lack of mitochondrial function in pgs1⌬ cells is the failure to translate gene products essential to the electron transport chain.

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Cardiolipin modulates the secondary structure of the presequence peptide of cytochrome oxidase subunit IV: a 2D ¹H‐NMR study

Cited by 27 publications

References 42 publications

The Active Streptococcal Hyaluronan Synthases (HASs) Contain a Single HAS Monomer and Multiple Cardiolipin Molecules

The Active Streptococcal Hyaluronan Synthases (HASs) Contain a Single HAS Monomer and Multiple Cardiolipin Molecules

The mitochondrial processing peptidase: Function and specificity

Lack of Mitochondrial Anionic Phospholipids Causes an Inhibition of Translation of Protein Components of the Electron Transport Chain

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Cardiolipin modulates the secondary structure of the presequence peptide of cytochrome oxidase subunit IV: a 2D 1H‐NMR study

Cited by 27 publications

References 42 publications

The Active Streptococcal Hyaluronan Synthases (HASs) Contain a Single HAS Monomer and Multiple Cardiolipin Molecules

The Active Streptococcal Hyaluronan Synthases (HASs) Contain a Single HAS Monomer and Multiple Cardiolipin Molecules

The mitochondrial processing peptidase: Function and specificity

Lack of Mitochondrial Anionic Phospholipids Causes an Inhibition of Translation of Protein Components of the Electron Transport Chain

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Cardiolipin modulates the secondary structure of the presequence peptide of cytochrome oxidase subunit IV: a 2D ¹H‐NMR study