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Pathway · 3 proteins

Metal installation

Scaffolds, carriers and chaperones help deliver metals to proteins.

How it works

  1. Iron-sulfur cluster assembly is represented by a scaffold protein and by ErpA, an insertion protein: the scaffold builds the cluster, and the insertion protein hands it to a recipient.
  2. HypA is a nickel metallochaperone used in hydrogenase maturation, and a PCu(A)C-family copper chaperone delivers copper to its targets. Both are delivery proteins, not enzymes of their own pathways.
  3. Delivery is what makes an imported metal useful. The recipients appear in the module below and in system 16, where cluster and metallocofactor assembly is described in more detail.

Grouped by the atlas’s curated pathway map. The table order is not a proven reaction order.

Its proteins

ProteinECReaction (UniProt)Metal or clusterAmino acidsCertainty
Copper chaperone PCu(A)C———151System only
Protein aq_1857———116Step named
Iron-sulfur cluster assembly scaffold protein IscU——[2Fe-2S] cluster157Step named

Also part of this pathway

These proteins are described under another pathway, but also take part here.

ProteinECReaction (UniProt)Metal or clusterAmino acidsCertainty
Hydrogenase maturation factor HypAHome: Not yet placed in a pathway——Ni(2+), Zn(2+)115Step named

Origins

How could iron-sulfur clusters and other metal centres be put into enzymes before assembly proteins existed?

Naturalistic proposal

Iron-sulfur minerals feature in metabolism-first proposals, but the books searched describe no prebiotic route by which clusters were loaded into proteins.

Design analysis

Iron-sulfur clusters are built on a scaffold protein from sulfur supplied by cysteine desulfurase, then handed to their target enzymes. In some cells the cluster even switches a protein's job: aconitase without its cluster becomes a regulator that binds messenger RNA to control iron use.

From the books: Nelson & Cox, Lehninger Principles of Biochemistry, p. 624.

The wider question for this part of the cell: origins for loading metals into enzymes.

Sources

Other pathways in this group: NiFe-hydrogenase maturation · Not yet placed in a pathway