2019
DOI: 10.1074/jbc.ra119.007716
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Mechanism of frataxin “bypass” in human iron–sulfur cluster biosynthesis with implications for Friedreich’s ataxia

Abstract: Antonio and multiple High-Performance Computing clusters were supported by National Science Foundation Extreme Science and Engineering Discovery Environment Grant MCB070038. The authors declare that they have no conflicts of interest with the contents of this article. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This article contains Table S1 and Figs. S1-S9.

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Cited by 21 publications
(16 citation statements)
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“…Consistently, we also observe a correlation between the amount of dimeric IscS and the rate of decay of the Cys-quinonoid intermediate (Fig. 7A), which is dependent on the ability of the mobile S-transfer loop to function as a proton donor (45)(46)(47)…”
Section: Substitutions Have Varied Effects On the Dimeric Binding Consupporting
confidence: 83%
“…Consistently, we also observe a correlation between the amount of dimeric IscS and the rate of decay of the Cys-quinonoid intermediate (Fig. 7A), which is dependent on the ability of the mobile S-transfer loop to function as a proton donor (45)(46)(47)…”
Section: Substitutions Have Varied Effects On the Dimeric Binding Consupporting
confidence: 83%
“…5, step I). This step was recently shown to be unaffected by FXN but accelerated for variants of ISCU2 (42). Interestingly, the FXN-dependent stimulation of [2Fe-2S] cluster synthesis and this FXN-independent acceleration of cluster transfer were shown to be additive, and both increase the overall Fe-S cluster flux through the pathway (42).…”
Section: Discussionmentioning
confidence: 92%
“…The truncated form, FXN Δ1-80 , has a modest binding affinity for iron (3 to 55 μM), which led to the proposal that FXN accelerates Fe-S cluster synthesis by functioning as a chaperone that donates iron (29)(30)(31)(32)(33)(34)(35)(36)(37)(38). More recently, multiple studies provide evidence that FXN enhances both the cysteine desulfurase activity (increasing the catalytic constant [k cat ] by ∼12-fold) and the subsequent Fe-S cluster assembly rate on the scaffold protein (5,22,(39)(40)(41)(42). Remarkably, both FXN and its prokaryotic homolog, CyaY, stimulate the in vitro Fe-S assembly reactions by the human Fe-S biosynthetic complex but inhibit the equivalent reaction by the prokaryotic system (43,44).…”
mentioning
confidence: 99%
“…The most probable sources of the necessary iron are the mitochondrial labile iron pool and frataxin, which can bind iron through acidic regions within the protein. Frataxin interacts with the ISCU–NSF1–ISD11 complex, and has been hypothesized to mediate iron’s entry into the ISC biogenesis scaffold and/or act as a modulator for NFS1 that might facilitate persulfide transfer to ISCU [ 208 , 221 , 236 , 237 , 238 , 239 , 240 , 241 , 242 , 243 ]. Decreased expression of frataxin impairs ISC biogenesis and iron metabolism, as seen in Friedreich’s ataxia [ 77 , 244 ].…”
Section: Sites Of Mitochondrial Iron Utilizationmentioning
confidence: 99%