Iron-sulfur cluster scaffold protein

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Iron-sulfur cluster scaffold protein
Iron-sulfur cluster scaffold protein
Ribbon model of the ISCU of the house mouse ( Mus musculus ), according to PDB  1WFZ
Properties of human protein
Mass / length primary structure 133 amino acids
Isoforms ISCU1, ISCU2
Identifier
Gene name ISCU
External IDs
Occurrence
Homology family ISCU
Parent taxon Chordates

The iron-sulfur cluster scaffold protein (ISCU) is a protein in chordates that is part of a protein complex that brings about the production of iron-sulfur clusters . These clusters are cofactors for several essential enzymes . In addition, ISCU serves as an independent transport protein for the clusters. There are two isoforms of protein located in the cytosol and in the mitochondria . In humans, ISCU is mainly produced in the heart , liver , skeletal muscle , brain , pancreas , kidneys , lungs and placenta . Mutations on ISCU - gene can, for lack of the protein, and this (rare) to the lack of the corresponding enzymes with myopathy lead.

function

Assembling the iron-sulfur cluster

ISCU is part of the complex that produces Fe-S clusters. ISCU takes on the role of binding the iron atoms that are transported by ISCA, while the enzyme cysteine ​​desulfurase provides sulfur atoms with cysteine ​​consumption . First, [2Fe-2S] is compiled, and finally [4Fe-4S] through dimerization. This process can take place in the mitochondria as well as in the cytosol, after which the finished [4Fe-4S] is transported into the plasma.

Cluster transport

After the cluster synthesis, ISCU transports it out of the mitochondrion. The corresponding membrane transporter is the ABC7 iron transporter ( TCDB : 3.A.1.210.4 ). It must be the only process that transports large amounts of iron out of the mitochondria, since both with ISCU deficiency and with ABCB7 deficiency iron accumulates in these organelles, which ultimately leads to their defect.

Individual evidence

  1. ↑ UniProt Q9H1K1
  2. ↑ a b Rouault TA, Tong WH: Iron-sulfur cluster biogenesis and human disease . In: Trends Genet. . 24, No. 8, August 2008, pp. 398-407. doi : 10.1016 / j.tig.2008.05.008 . PMID 18606475 . PMC 2574672 (free full text).
  3. ↑ Chandramouli K, Unciuleac MC, Naik S, Dean DR, Huynh BH, Johnson MK: Formation and properties of [4Fe-4S] clusters on the IscU scaffold protein . In: Biochemistry . 46, No. 23, June 2007, pp. 6804-11. doi : 10.1021 / bi6026659 . PMID 17506525 .
  4. ↑ Yang J, Bitoun JP, Ding H: Interplay of IscA and IscU in biogenesis of iron-sulfur clusters . In: J. Biol. Chem. . 281, No. 38, September 2006, pp. 27956-63. doi : 10.1074 / jbc.M601356200 . PMID 16877383 .