Journal article

Publication year: 2023

Journal: Proceedings of the National Academy of Sciences

Volume number: 120

Issue number: 44

ISSN: 0027-8424

eISSN: 1091-6490

Open access status: Hybrid

DOI Link: https://doi.org/10.1073/pnas.2311057120

Publisher: National Academy of Sciences

Abstract: 
The eukaryotic cytosolic Fe-S protein assembly (CIA) machinery inserts iron-sulfur (Fe-S) clusters into cytosolic and nuclear proteins. In the final maturation step, the Fe-S cluster is transferred to the apo-proteins by the CIA-targeting complex (CTC). However, the molecular recognition determinants of client proteins are unknown. We show that a conserved [LIM]-[DES]-[WF]-COO-tripeptide is present at the C-terminus of more than a quarter of clients or their adaptors. When present, this targeting complex recognition (TCR) motif is necessary and sufficient for binding to the CTC in vitro and for directing Fe-S cluster delivery in vivo. Remarkably, fusion of this TCR signal enables engineering of cluster maturation on a nonnative protein via recruitment of the CIA machinery. Our study advances our understanding of Fe-S protein maturation and paves the way for bioengineering novel pathways containing Fe-S enzymes.

Harvard Citation style: Marquez, M., Greth, C., Buzuk, A., Liu, Y., Blinn, C., Beller, S., et al. (2023) Cytosolic iron-sulfur protein assembly system identifies clients by a C-terminal tripeptide, Proceedings of the National Academy of Sciences, 120(44), Article e2311057120. https://doi.org/10.1073/pnas.2311057120

APA Citation style: Marquez, M., Greth, C., Buzuk, A., Liu, Y., Blinn, C., Beller, S., Leiskau, L., Hushka, A., Wu, K., Nur, K., Netz, D., Perlstein, D., & Pierik, A. (2023). Cytosolic iron-sulfur protein assembly system identifies clients by a C-terminal tripeptide. Proceedings of the National Academy of Sciences. 120(44), Article e2311057120. https://doi.org/10.1073/pnas.2311057120