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Structure paper

TitleMETTL17 is an Fe-S cluster checkpoint for mitochondrial translation.
Journal, issue, pagesMol Cell, Vol. 84, Issue 2, Page 359-374.e8, Year 2024
Publish dateJan 18, 2024
AuthorsTslil Ast / Yuzuru Itoh / Shayan Sadre / Jason G McCoy / Gil Namkoong / Jordan C Wengrod / Ivan Chicherin / Pallavi R Joshi / Piotr Kamenski / Daniel L M Suess / Alexey Amunts / Vamsi K Mootha /
PubMed AbstractFriedreich's ataxia (FA) is a debilitating, multisystemic disease caused by the depletion of frataxin (FXN), a mitochondrial iron-sulfur (Fe-S) cluster biogenesis factor. To understand the cellular ...Friedreich's ataxia (FA) is a debilitating, multisystemic disease caused by the depletion of frataxin (FXN), a mitochondrial iron-sulfur (Fe-S) cluster biogenesis factor. To understand the cellular pathogenesis of FA, we performed quantitative proteomics in FXN-deficient human cells. Nearly every annotated Fe-S cluster-containing protein was depleted, indicating that as a rule, cluster binding confers stability to Fe-S proteins. We also observed depletion of a small mitoribosomal assembly factor METTL17 and evidence of impaired mitochondrial translation. Using comparative sequence analysis, mutagenesis, biochemistry, and cryoelectron microscopy, we show that METTL17 binds to the mitoribosomal small subunit during late assembly and harbors a previously unrecognized [FeS] cluster required for its stability. METTL17 overexpression rescued the mitochondrial translation and bioenergetic defects, but not the cellular growth, of FXN-depleted cells. These findings suggest that METTL17 acts as an Fe-S cluster checkpoint, promoting translation of Fe-S cluster-rich oxidative phosphorylation (OXPHOS) proteins only when Fe-S cofactors are replete.
External linksMol Cell / PubMed:38199006 / PubMed Central
MethodsEM (single particle)
Resolution2.25 - 2.87 Å
Structure data

16966

8om2

EMDB-16966, PDB-8om2:
Small subunit of yeast mitochondrial ribosome in complex with METTL17/Rsm22.
Method: EM (single particle) / Resolution: 2.57 Å

16967

8om3

EMDB-16967, PDB-8om3:
Small subunit of yeast mitochondrial ribosome in complex with IF3/Aim23.
Method: EM (single particle) / Resolution: 2.87 Å

16968

8om4

EMDB-16968, PDB-8om4:
Small subunit of yeast mitochondrial ribosome.
Method: EM (single particle) / Resolution: 2.32 Å

EMDB-17089: Small subunit of yeast mitochondrial ribosome in complex with METTL17/Rsm22 (overall refinement)
Method: EM (single particle) / Resolution: 2.57 Å

EMDB-17090: Small subunit of yeast mitochondrial ribosome in complex with METTL17/Rsm22 (local-masked refined on the body)
Method: EM (single particle) / Resolution: 2.47 Å

EMDB-17091: Small subunit of yeast mitochondrial ribosome in complex with METTL17/Rsm22 (local-masked refined on the head)
Method: EM (single particle) / Resolution: 2.51 Å

EMDB-17092: Small subunit of yeast mitochondrial ribosome in complex with METTL17/Rsm22 (local-masked refined on the tail)
Method: EM (single particle) / Resolution: 2.49 Å

EMDB-17093: Small subunit of yeast mitochondrial ribosome in complex with METTL17/Rsm22 (local-masked refined on METTL17/Rsm22)
Method: EM (single particle) / Resolution: 2.77 Å

EMDB-17094: Small subunit of yeast mitochondrial ribosome in complex with IF3/Aim23 (overall refinement)
Method: EM (single particle) / Resolution: 2.87 Å

EMDB-17095: Small subunit of yeast mitochondrial ribosome in complex with IF3/Aim23 (local-masked refined on the body)
Method: EM (single particle) / Resolution: 2.71 Å

EMDB-17096: Small subunit of yeast mitochondrial ribosome in complex with IF3/Aim23 (local-masked refined on the head)
Method: EM (single particle) / Resolution: 2.71 Å

EMDB-17097: Small subunit of yeast mitochondrial ribosome in complex with IF3/Aim23 (local-masked refined on the tail)
Method: EM (single particle) / Resolution: 2.77 Å

EMDB-17098: Small subunit of yeast mitochondrial ribosome (overall refinement)
Method: EM (single particle) / Resolution: 2.32 Å

EMDB-17099: Small subunit of yeast mitochondrial ribosome (local-masked refined on the body)
Method: EM (single particle) / Resolution: 2.25 Å

EMDB-17100: Small subunit of yeast mitochondrial ribosome(local-masked refined on the head)
Method: EM (single particle) / Resolution: 2.28 Å

EMDB-17101: Small subunit of yeast mitochondrial ribosome(local-masked refined on the tail)
Method: EM (single particle) / Resolution: 2.28 Å

EMDB-17102: Small subunit of yeast mitochondrial ribosome(local-masked refined on the helix bundle)
Method: EM (single particle) / Resolution: 2.29 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-K:
Unknown entry

ChemComp-LMT:
DODECYL-BETA-D-MALTOSIDE / detergent*YM

ChemComp-ATP:
ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying molecule*YM / Adenosine triphosphate

ChemComp-SF4:
IRON/SULFUR CLUSTER / Iron–sulfur cluster

ChemComp-HOH:
WATER / Water

Source
  • saccharomyces cerevisiae (brewer's yeast)
KeywordsRIBOSOME / mitochondria / assembly / biogenesis / iron-sulfur cluster / 4Fe-4S / initiation factor 3 / pre-initiation complex

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