ABCMdb

ABCB7 p.Leu144Ala

Predicted by SNAP2:	A: N (82%), C: N (82%), D: D (75%), E: D (71%), F: N (87%), G: D (59%), H: D (63%), I: N (93%), K: D (71%), M: N (93%), N: D (71%), P: D (75%), Q: D (63%), R: D (71%), S: N (53%), T: N (57%), V: N (93%), W: D (66%), Y: D (63%),
Predicted by PROVEAN:	A: D, C: D, D: D, E: D, F: D, G: D, H: D, I: N, K: D, M: N, N: D, P: D, Q: D, R: D, S: D, T: D, V: N, W: D, Y: D,

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Publications
[hide] Leucine biosynthesis regulates cytoplasmic iron-su... J Biol Chem. 2011 Nov 25;286(47):40878-88. Epub 2011 Sep 16. Bedekovics T, Li H, Gajdos GB, Isaya G
Leucine biosynthesis regulates cytoplasmic iron-sulfur enzyme biogenesis in an Atm1p-independent manner.
J Biol Chem. 2011 Nov 25;286(47):40878-88. Epub 2011 Sep 16., [PMID:21926174]

Abstract [show]
Fe-S clusters (ISCs) are versatile cofactors utilized by many mitochondrial, cytoplasmic, and nuclear enzymes. Whereas mitochondria can independently initiate and complete ISC synthesis, other cellular compartments are believed to assemble ISCs from putative precursors exported from the mitochondria via an ATP binding cassette (ABC) transporter conserved from yeast (Atm1p) to humans (ABCB7). However, the regulatory interactions between mitochondrial and extramitochondrial ISC synthesis are largely unknown. In yeast, we found that mitochondrial ISC synthesis is regulated by the leucine biosynthetic pathway, which among other proteins involves an abundant cytoplasmic [4Fe-4S] enzyme, Leu1p. Enzymatic blocks in the pathway (i.e. leu1Delta or leu2Delta gene deletion mutations) induced post-transcriptional up-regulation of core components of mitochondrial ISC biosynthesis (i.e. the sulfur donor Nfs1p, the iron donor Yfh1p, and the ISC scaffold Isu1p). In leu2Delta cells, transcriptional mechanisms also led to dramatic up-regulation of Leu1p with concomitant down-regulation of mitochondrial aconitase (Aco1p), a [4Fe-4S] enzyme in the tricarboxylic acid cycle. Accordingly, the leu2Delta deletion mutation exacerbated Aco1p inactivation in cells with mutations in Yfh1p. These data indicate that defects in leucine biosynthesis promote the biogenesis of enzymatically active Leu1p at the expense of Aco1p activity. Surprisingly, this effect is independent of Atm1p; previous reports linking the loss of Leu1p activity to Atm1p depletion were confounded by the fact that LEU2 was used as a selectable marker to create Atm1p-depleted cells, whereas a leu2Delta allele was present in Atm1p-repleted controls. Thus, still largely unknown transcriptional and post-transcriptional mechanisms control ISC distribution between mitochondria and other cellular compartments.

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95 We selected point mutations in Yfh1p (Y73A, L144A, and V150A) that did not result in obvious phenotypes when yeast cells grew logarithmically in rich medium (Ref. 21 and data not shown). Login to comment
138 YFH1leu2⌬MAT␣ura3-52lys2-801amber ade2-101ochre trp1-⌬63his3-⌬200leu2-⌬1yfh1⌬::HIS3ϩYCplac22-YFH1-TRP1[␳ϩ ]21 yfh1Y73A leu2⌬MAT␣ura3-52lys2-801amber ade2-101ochre trp1-⌬63his3-⌬200leu2-⌬1yfh1⌬::HIS3ϩpRSGPD-YFH1[Y73A][␳ϩ ]21 yfh1L144A leu2⌬MAT␣ura3-52lys2-801amber ade2-101ochre trp1-⌬63his3-⌬200leu2-⌬1yfh1⌬::HIS3ϩpRSGPD-YFH1[L144A][␳ϩ ]Thisstudy yfh1L144A LEU2(2␮m)MAT423;ura3-52lys2-801amber ade2-101ochre trp1-⌬63his3-⌬200leu2-⌬1yfh1⌬::HIS3ϩpRSGPD-YFH1[L144A][␳ϩ ]ϩYep24-LEU2-URA3Thisstudy yfh1V150A leu2⌬MAT␣ura3-52lys2-801amber ade2-101ochre trp1-⌬63his3-⌬200leu2-⌬1yfh1⌬::HIS3ϩpRSGPD-YFH1[V150A][␳ϩ ]Thisstudy yfh1V150A LEU2(2␮m)MAT␣ura3-52lys2-801amber ade2-101ochre trp1-⌬63his3-⌬200leu2-⌬1yfh1⌬::HIS3ϩpRSGPD-YFH1[V150A][␳ϩ ]ϩYep24-LEU2-URA3Thisstudy YFH1LEU2MAT␣ura3-52lys2-801amber ade2-101ochre trp1-⌬63his3-⌬200yfh1⌬::HIS3ϩYCplac22-YFH1-TRP1[␳ϩ ]Thisstudy yfh1Y73A LEU2MAT␣ura3-52lys2-801amber ade2-101ochre trp1-⌬63his3-⌬200yfh1⌬::HIS3ϩpRSGPD-YFH1[Y73A][␳ϩ ]Thisstudy yfh1Y73A LEU2(CEN)MAT␣ura3-52lys2-801amber ade2-101ochre trp1-⌬63his3-⌬200yfh1⌬::HIS3ϩpRSGPD-YFH1[Y73A][␳ϩ ]ϩpRS415-LEU2Thisstudy yfh1Y73A LEU2(2␮m)MAT␣ura3-52lys2-801amber ade2-101ochre trp1-⌬63his3-⌬200yfh1⌬::HIS3ϩpRSGPD-YFH1[Y73A][␳ϩ ]ϩYep24-LEU2-URA3Thisstudy YFH1LEU1-FLAGLEU2-FLAGMAT␣ura3-52lys2-801amber ade2-101ochre trp1-⌬63his3-⌬200yfh1⌬::HIS3ϩYCplac22-YFH1-TRP1[␳ϩ ]LEU1-FLAGLEU2-FLAGThisstudy yfh1Y73A LEU1-FLAGLEU2-FLAGMAT␣ura3-52lys2-801amber ade2-101ochre trp1-⌬63his3-⌬200yfh1⌬::HIS3ϩpRSGPD-YFH1[Y73A][␳ϩ ]LEU1-FLAGLEU2-FLAGThisstudy YFH1leu1⌬LEU2-FLAGMAT␣ura3-52lys2-801amber ade2-101ochre trp1-⌬63his3-⌬200yfh1⌬::HIS3ϩYCplac22-YFH1-TRP1[␳ϩ ]leu1⌬::KanMX4LEU2-FLAGThisstudy yfh1Y73A leu1⌬LEU2(CEN)MAT␣ura3-52lys2-801amber ade2-101ochre trp1-⌬63his3-⌬200yfh1⌬::HIS3ϩpRSGPD-YFH1[Y73A][␳ϩ ]leu1⌬::KanMX4ϩpRS415-LEU2Thisstudy yfh1Y73A leu1⌬LEU2(2␮m)MAT␣ura3-52lys2-801amber ade2-101ochre trp1-⌬63his3-⌬200yfh1⌬::HIS3ϩpRSGPD-YFH1[Y73A][␳ϩ ]leu1⌬::KanMX4ϩYep24-LEU2-URA3Thisstudy yfh1Y73A leu1⌬LEU2-FLAGMAT␣ura3-52lys2-801amber ade2-101ochre trp1-⌬63his3-⌬200yfh1⌬::HIS3ϩpRSGPD-YFH1[Y73A][␳ϩ ]leu1⌬::KanMX4LEU2-FLAGThisstudy YFH1LEU1-FLAGleu2⌬MAT␣ura3-52lys2-801amber ade2-101ochre trp1-⌬63his3-⌬200yfh1⌬::HIS3ϩYCplac22-YFH1-TRP1[␳ϩ ]LEU1-FLAGleu2⌬::KanMX4Thisstudy yfh1Y73A LEU1-FLAGleu2⌬MAT␣ura3-52lys2-801amber ade2-101ochre trp1-⌬63his3-⌬200yfh1⌬::HIS3ϩpRSGPD-YFH1[Y73A][␳ϩ ]LEU1-FLAGleu2⌬::KanMX4Thisstudy YFH1LEU1-FLAGLEU2-FLAGleu3⌬MAT␣ura3-52lys2-801amber ade2-101ochre trp1-⌬63his3-⌬200yfh1⌬::HIS3ϩYCplac22-YFH1-TRP1[␳ϩ ]LEU1-FLAGLEU2-FLAGleu3⌬::URA3Thisstudy yfh1Y73A LEU1-FLAGLEU2-FLAGleu3⌬MAT␣ura3-52lys2-801amber ade2-101ochre trp1-⌬63his3-⌬200yfh1⌬::HIS3ϩpRSGPD-YFH1[Y73A][␳ϩ ]LEU1-FLAGLEU2-FLAGleu3⌬::URA3Thisstudy YFH1leu1⌬-LEU2-FLAGleu3⌬MAT␣ura3-52lys2-801amber ade2-101ochre trp1-⌬63his3-⌬200yfh1⌬::HIS3ϩYCplac22-YFH1-TRP1[␳ϩ ]leu1⌬::KanMX4LEU2-FLAGleu3⌬::URA3Thisstudy yfh1Y73A leu1⌬-LEU2-FLAGleu3⌬MAT␣ura3-52lys2-801amber ade2-101ochre trp1-⌬63his3-⌬200yfh1⌬::HIS3ϩpRSGPD-YFH1[Y73A][␳ϩ ]leu1⌬::KanMX4LEU2-FLAGleu3⌬::URA3Thisstudy YFH1LEU1-FLAGleu2⌬leu3⌬MAT␣ura3-52lys2-801amber ade2-101ochre trp1-⌬63his3-⌬200yfh1⌬::HIS3ϩYCplac22-YFH1-TRP1[␳ϩ ]LEU1-FLAGleu2⌬::KanMX4leu3⌬::URA3Thisstudy yfh1Y73A LEU1-FLAGleu2⌬leu3⌬MAT␣ura3-52lys2-801amber ade2-101ochre trp1-⌬63his3-⌬200yfh1⌬::HIS3ϩpRSGPD-YFH1[Y73A][␳ϩ ]LEU1-FLAGleu2⌬::KanMX4leu3⌬::URA3Thisstudy YFH1leu1⌬LEU2-FLAGleu3⌬MAT␣ura3-52lys2-801amber ade2-101ochre trp1-⌬63his3-⌬200yfh1⌬::HIS3ϩYCplac22-YFH1[Y73A]-TRP1[␳ϩ ]leu1⌬::KanMX4LEU2-FLAGleu3⌬::URA3Thisstudy yfh1Y73A leu1⌬LEU2-FLAGleu3⌬MAT␣ura3-52lys2-801amber ade2-101ochre trp1-⌬63his3-⌬200yfh1⌬::HIS3ϩpRSGPD-YFH1[Y73A][␳ϩ ]leu1⌬::KanMX4LEU2-FLAGleu3⌬::URA3Thisstudy yfh1Y73A leu2⌬aco1⌬MAT␣ura3-52lys2-801amber ade2-101ochre trp1-⌬63his3-⌬200leu2-⌬1yfh1⌬::HIS3ϩpRSGPD-YFH1[Y73A][␳ϩ ]Aco1⌬::KanMX4Thisstudy yfh1Y73 LEU2aco1⌬MAT␣ura3-52lys2-801amber ade2-101ochre trp1-⌬63his3-⌬200yfh1⌬::HIS3ϩYCplac22-YFH1[Y73A]-TRP1[␳ϩ ]Aco1⌬::KanMX4Thisstudy LEU2ATM1MAT␣ura3-52lys2-801amber ade2-101ochre trp1-⌬63his3-⌬200yfh1⌬::HIS3ϩYCplac22-YFH1-TRP1[␳ϩ ]ATM1-FLAG3-URA3Thisstudy leu2⌬ATM1MAT␣ura3-52lys2-801amber ade2-101ochre trp1-⌬63his3-⌬200leu2-⌬1yfh1⌬::HIS3ϩYCplac22-YFH1-TRP1[␳ϩ ]ATM1-FLAG3-URA3Thisstudy LEU2Gal-ATM1MAT␣ura3-52lys2-801amber ade2-101ochre trp1-⌬63his3-⌬200yfh1⌬::HIS3ϩYCplac22-YFH1-TRP1[␳ϩ ]KanMX4-Gal-ATM1-FLAG3-URA3Thisstudy leu2⌬Gal-ATM1MAT␣ura3-52lys2-801amber ade2-101ochre trp1-⌬63his3-⌬200leu2-⌬1yfh1⌬::HIS3ϩYCplac22-YFH1-TRP1[␳ϩ ]KanMX4-Gal-ATM1-FLAG3-URA3Thisstudy LEU1-FLAGLEU2-FLAGATM1MAT␣ura3-52lys2-801amber ade2-101ochre trp1-⌬63his3-⌬200yfh1⌬::HIS3ϩYCplac22-YFH1-TRP1[␳ϩ ]LEU1-FLAGLEU2-FLAGATM1-FLAG3-URA3Thisstudy LEU1-FLAGleu2⌬ATM1MAT␣ura3-52lys2-801amber ade2-101ochre trp1-⌬63his3-⌬200leu2-⌬1yfh1⌬::HIS3ϩYCplac22-YFH1-TRP1[␳ϩ ]LEU1-FLAGATM1-FLAG3-URA3Thisstudy LEU1-FLAGLEU2-FLAGGal-ATM1MAT␣ura3-52lys2-801amber ade2-101ochre trp1-⌬63his3-⌬200yfh1⌬::HIS3ϩYCplac22-YFH1-TRP1[␳ϩ ]LEU1-FLAGLEU2-FLAGKanMX4-Gal-ATM1-FLAG3-URA3Thisstudy LEU1-FLAGleu2⌬Gal-ATM1MAT␣ura3-52lys2-801amber ade2-101ochre trp1-⌬63his3-⌬200leu2-⌬1yfh1⌬::HIS3ϩYCplac22-YFH1-TRP1[␳ϩ ]LEU1-FLAGKanMX4-Gal-ATM1-FLAG3-URA3Thisstudy Leucine Synthesis Controls ISC Assembly 40882 cally active Leu1p. 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