9UKY

Crystal structure of dmCIAO1-CIAO2B-hCDKAL1 pentapeptide complex

Summary for 9UKY

• Entry DOI: 10.2210/pdb9uky/pdb
• Descriptor: MIP18 family protein galla-2, Probable cytosolic iron-sulfur protein assembly protein Ciao1 (3 entities in total)
• Functional Keywords: fe-s proteins, pentapeptide, consensus motif, ctc, metal binding protein
• Biological source: Drosophila melanogaster (fruit fly); More
• Total number of polymer chains: 2
• Total formula weight: 54856.21

Authors

Ren, W.J.,Yang, W.,Wang, H. (deposition date: 2025-04-18, release date: 2025-12-24, Last modification date: 2026-07-08)

Primary citation

Ren, W.,Huang, Y.,Hu, M.,Yang, Y.,Yang, W.,Wang, H.
Client recruitment mechanism of the cytosolic Fe-S cluster assembly targeting complex.
Embo J., 45:1264-1291, 2026

PubMed Abstract: Most cytosolic and nuclear eukaryotic Fe-S proteins acquire their critical Fe-S cofactor by interacting with the cytosolic Fe-S cluster assembly targeting complex (CTC). Despite the critical roles these Fe-S proteins play in fundamental biology, how they are specifically recognized by the CTC remains largely understudied. Here we identified a hidden consensus pentapeptide motif as a sequence signature dictating cluster acquisition in a majority of known human Fe-S proteins, particularly DNA/RNA processing enzymes for genome maintenance. The presence of this motif drives CTC-client engagement, while its defect impairs CTC recognition, iron incorporation, and enzymatic activities of these clients, ultimately compromising their cellular functions, such as in DNA repair. Furthermore, our studies revealed a conserved surface pocket of CTC dedicated to client recruitment in general. This single pocket recognizes two distinct sequence signatures in clients including the Pentapeptide motif and a previously reported C-tail motif. Subsequent structure-guided affinity-purification mass spectrometry (AP-MS) enabled us to investigate the pocket-dependent human CTC interactome, potentially unveiling unrecognized Fe-S proteins. Overall, our findings decipher the sequence signature-directed mechanism underlying CTC client recruitment and open an avenue for expanding the repertoire of Fe-S proteins.

PubMed: 41484370
DOI: 10.1038/s44318-025-00676-x

Experimental method

X-RAY DIFFRACTION (2.5 Å)