Cracking the CIA code: apo-client identification by the cytosolic iron sulfur cluster assembly (CIA) system

Seminar Details

Host: Dr. Paul Lindahl

Time: 4:00pm-5:00pm

Location: BICH Rm 108

Seminar Abstract

The cytosolic iron sulfur cluster assembly (CIA) pathway matures cytosolic and nuclear iron sulfur (Fe-S) proteins essential for life sustaining processes including DNA replication and repair, transcription, and translation. In the final step of the pathway, the CIA targeting complex (CTC) recognizes apo-clients and inserts their Fe-S cofactors, but the molecular signals guiding CTC to its clients have been challenging to decipher. In late 2023, we reported that C-terminal tripeptide, called the targeting complex recognition motif, is necessary and sufficient to direct Fe-S delivery from the CTC to 20-25% of CIA clients.1 In this talk, I will present a progress report on our work to understand the molecular basis for recognition of the targeting peptide by the CTC. By quantitatively mapping the peptide-protein interaction, we have discovered which elements of the TCR tripeptide are most critical for recruitment of the targeting complex and identified additional TCR peptide sequences. Using a combination of computational, biophysical, and biochemical approaches, we have determined that the targeting motif docks at the interface of the Cia1 and Cia2 subunits of the targeting complex. Our study fills a critical gap in our molecular level understanding of how Fe-S biogenesis systems identify their clients and a roadmap for discovering additional short linear peptide motifs controlling metallocluster delivery by the CIA system. 1 Marquez MD, Greth C, Buzuk A, Liu Y, Blinn CM, Beller S, Leiskau L, Hushka A, Wu K, Nur K, Netz DJA, Perlstein DL, Pierik AJ. Cytosolic iron-sulfur protein assembly system identifies clients by a C-terminal tripeptide. Proc Natl Acad Sci U S A. 2023 120(44):e2311057120. doi: 10.1073/pnas.2311057120. Epub 2023 Oct 26. PMID: 37883440; PMCID: PMC10623007.