Falcon (Edison) deep research report: SSQ1 (Q05931), mitochondrial Hsp70 chaperone for Fe-S cluster biogenesis
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Ssq1 is a specialized, ATP-dependent mitochondrial Hsp70 chaperone that
drives the Fe-S cluster transfer step: it promotes release of a newly
assembled [2Fe-2S] cluster from the Isu1/Isu2 scaffold and hands it off to
the carrier Grx5, rather than synthesizing the cluster itself.
"**Ssq1 is an ATP-dependent Hsp70 chaperone/ATPase that drives the ISC “transfer step”**: it promotes **release of a newly assembled Fe–S cluster from the Isu scaffold** and facilitates **handoff** to downstream factors (notably Grx5), enabling maturation of mitochondrial Fe–S proteins and supporting downstream cytosolic/nuclear Fe–S biogenesis"
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Substrate specificity is achieved by recognition of the conserved LPPVK
peptide motif of the Isu1 scaffold at the Hsp70 substrate-binding site;
Grx5 binds a distinct site and does not stimulate ATPase, allowing
simultaneous Isu1+Grx5 occupancy for cluster handoff.
"**Grx5 binds Ssq1 at a distinct site** (not displaced by excess LPPVK peptide) and **does not stimulate Ssq1 ATPase**, enabling simultaneous Isu1+Grx5 association on Ssq1 for handoff"
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The chaperone cycle is driven by the J-protein Jac1 (recruits Isu1 and
synergistically stimulates Ssq1 ATPase) and reset by the nucleotide
exchange factor Mge1.
"The **J-domain cochaperone Jac1** recruits the Fe–S-loaded scaffold and stimulates Ssq1 ATP hydrolysis; Jac1 and Isu1 act **synergistically** to stimulate Ssq1 ATPase activity"
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Ssq1 and Jac1 localize to the mitochondrial matrix; ssq1 loss causes
~10-fold mitochondrial iron accumulation and reduced activity of Fe-S
enzymes (aconitase, succinate dehydrogenase, cytochrome bc1).
"**Decreased activities** of Fe–S enzymes/proteins including **aconitase**, **cytochrome bc1 complex**, and **succinate dehydrogenase** in ssq1/jac1 mutants"
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Ssq1 is a low-abundance, highly specialized Hsp70 distinct from the
general mtHsp70 Ssc1; it is ~500-1000-fold less abundant than Ssc1 and has
a narrowly defined native client (the Isu scaffold).
"Ssq1 represents a rare example of a **highly specialized Hsp70 system with a narrowly defined native client (the ISC scaffold Isu)**, supporting the view that Ssq1’s primary function is to catalyze a specific Fe–S transfer step rather than general mitochondrial proteostasis"
Gene Ontology annotation through association of InterPro records with GO terms
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
Jac1, a mitochondrial J-type chaperone, is involved in the biogenesis of Fe/S clusters in Saccharomyces cerevisiae.
The mitochondrial proteins Ssq1 and Jac1 are required for the assembly of iron sulfur clusters in mitochondria.
The two mitochondrial heat shock proteins 70, Ssc1 and Ssq1, compete for the cochaperone Mge1.
Ssq1, a mitochondrial Hsp70 involved in iron-sulfur (Fe/S) center biogenesis. Similarities to and differences from its bacterial counterpart.
An interaction between frataxin and Isu1/Nfs1 that is crucial for Fe/S cluster synthesis on Isu1.
Global landscape of protein complexes in the yeast Saccharomyces cerevisiae.
Toward the complete yeast mitochondrial proteome: multidimensional separation techniques for mitochondrial proteomics.
An atlas of chaperone-protein interactions in Saccharomyces cerevisiae: implications to protein folding pathways in the cell.
Quantitative variations of the mitochondrial proteome and phosphoproteome during fermentative and respiratory growth in Saccharomyces cerevisiae.
The social and structural architecture of the yeast protein interactome.
The cold sensitivity of a mutant of Saccharomyces cerevisiae lacking a mitochondrial heat shock protein 70 is suppressed by loss of mitochondrial DNA.
Mt-Hsp70 homolog, Ssc2p, required for maturation of yeast frataxin and mitochondrial iron homeostasis.
Suppressors of superoxide dismutase (SOD1) deficiency in Saccharomyces cerevisiae. Identification of proteins predicted to mediate iron-sulfur cluster assembly.
Role of the mitochondrial Hsp70s, Ssc1 and Ssq1, in the maturation of Yfh1.
The Hsp70 chaperone Ssq1p is dispensable for iron-sulfur cluster formation on the scaffold protein Isu1p.
The mitochondrial Hsp70 chaperone Ssq1 facilitates Fe/S cluster transfer from Isu1 to Grx5 by complex formation.
Co-evolution-driven switch of J-protein specificity towards an Hsp70 partner.
Iron-Sulfur Cluster Biogenesis Chaperones: Evidence for Emergence of Mutational Robustness of a Highly Specific Protein-Protein Interaction.