# Structure and Mechanism of the Human FE-S Cluster Assembly Complex

> **NIH NIH R01** · TEXAS A&M UNIVERSITY · 2022 · $292,186

## Abstract

Metal ions are essential to life as they augment amino acid protein
chemistry and thereby catalyze many difficult biological reactions. As “free” metal
ions are toxic and indiscriminately reactive, critical protein systems have evolved
to sequester, chaperone, and regulate metal ion concentrations. Defects in these
systems lead to metal ion metabolic disease and result in cellular, tissue, and
systemic pathology. The iron-sulfur cluster assembly pathway contains a
conserved set of metallochaperone proteins that recognize and insert Fe-S
clusters into apo metalloproteins. We determined the first crystal structure for the
NFS1-ISD11-ACP cysteine desulfurase, which is a central enzyme in this
pathway that is also implicated in providing sulfur for molybdenum cofactor
biosynthesis and tRNA modifications. Interestingly, three distinct interchangeable
α2β22 architectures are now known for the cysteine desulfurase complex that
have superimposable protomers but distinct protein-protein interactions. In this
proposal, we aim to investigate the functional relationship between these
architectures, elucidate mechanistic details for sulfur transfer to different acceptor
proteins and for Fe-S cluster assembly, and provide new insight into the
regulatory control mechanisms for human Fe-S cluster biosynthesis. This
fundamental research will establish a framework for emerging genetic results and
discoveries and provide a basis for understanding defects in iron-sulfur cluster
metabolism relevant to human health and disease.

## Key facts

- **NIH application ID:** 10437014
- **Project number:** 5R01GM096100-10
- **Recipient organization:** TEXAS A&M UNIVERSITY
- **Principal Investigator:** DAVID P BARONDEAU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $292,186
- **Award type:** 5
- **Project period:** 2011-09-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10437014

## Citation

> US National Institutes of Health, RePORTER application 10437014, Structure and Mechanism of the Human FE-S Cluster Assembly Complex (5R01GM096100-10). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10437014. Licensed CC0.

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