6TBL

Crystal structure of MMS19(CTD)-CIAO1-CIAO2B CIA targeting complex

Summary for 6TBL

• Entry DOI: 10.2210/pdb6tbl/pdb
• Descriptor: MMS19 nucleotide excision repair protein homolog, MIP18 family protein galla-2, Probable cytosolic iron-sulfur protein assembly protein Ciao1, ... (6 entities in total)
• Functional Keywords: fe-s cluster, fe-s, cia, cia targeting complex, biosynthetic protein
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 6
• Total formula weight: 137583.28

Authors

Kassube, S.A.,Thoma, N.H. (deposition date: 2019-11-01, release date: 2020-07-29, Last modification date: 2024-05-01)

Primary citation

Kassube, S.A.,Thoma, N.H.
Structural insights into Fe-S protein biogenesis by the CIA targeting complex.
Nat.Struct.Mol.Biol., 27:735-742, 2020

PubMed Abstract: The cytosolic iron-sulfur (Fe-S) assembly (CIA) pathway is required for the insertion of Fe-S clusters into cytosolic and nuclear client proteins, including many DNA replication and repair factors. The molecular mechanisms of client protein recognition and Fe-S cluster transfer remain unknown. Here, we report crystal structures of the CIA targeting complex (CTC), revealing that its CIAO2B subunit is centrally located and bridges CIAO1 and the client adaptor protein MMS19. Cryo-EM reconstructions of human CTC bound either to the DNA replication factor primase or to the DNA helicase DNA2, combined with biochemical, biophysical and yeast complementation assays, reveal an evolutionarily conserved, bipartite client recognition mode facilitated by CIAO1 and the structural flexibility of the MMS19 subunit. Unexpectedly, the primase Fe-S cluster is located ~70 Å away from the CTC reactive cysteine, implicating conformational dynamics of the CTC or additional maturation factors in the mechanism of Fe-S cluster transfer.

PubMed: 32632277
DOI: 10.1038/s41594-020-0454-0

Experimental method

X-RAY DIFFRACTION (2.65 Å)