Structural organization of essential iron-sulfur clusters in the evolutionarily highly conserved ATP-binding cassette protein ABCE1

Barthelme, Dominik, Scheele, Urte, Dinkelaker, Stephanie, Janoschka, Adam, Macmillan, Fraser, Albers, Sonja-Vernea, Driessen, Arnold J. M., Stagni, Marco Salamone, Bill, Eckhard, Meyer-Klaucke, Wolfram, Schunemann, Volker and Tampe, Robert (2007) Structural organization of essential iron-sulfur clusters in the evolutionarily highly conserved ATP-binding cassette protein ABCE1. Journal of Biological Chemistry, 282 (19). pp. 14598-14607. ISSN 0021-9258

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Abstract

The ABC protein ABCE1, formerly named RNase L inhibitor RLI1, is one of the most conserved proteins in evolution and is expressed in all organisms except eubacteria. Because of its fundamental role in translation initiation and/or ribosome biosynthesis, ABCE1 is essential for life. Its molecular mechanism has, however, not been elucidated. In addition to two ABC ATPase domains, ABCE1 contains a unique N-terminal region with eight conserved cysteines, predicted to coordinate iron-sulfur clusters. Here we present detailed information on the type and on the structural organization of the Fe-S clusters in ABCE1. Based on biophysical, biochemical, and yeast genetic analyses, ABCE1 harbors two essential diamagnetic [4Fe-4S](2+) clusters with different electronic environments, one ferredoxin-like (CPXnCX2CX2C; Cys at positions 4-7) and one unique ABCE1-type cluster (CXPX2CX3CXnCP; Cys at positions 1, 2, 3, and 8). Strikingly, only seven of the eight conserved cysteines coordinating the Fe-S clusters are essential for cell viability. Mutagenesis of the cysteine at position 6 yielded a functional ABCE1 with the ferredoxin-like Fe-S cluster in a paramagnetic [3Fe-4S](+) state. Notably, a lethal mutation of the cysteine at position 4 can be rescued by ligand swapping with an adjacent, extra cysteine conserved among all eukaryotes.

Item Type: Article
Faculty \ School: Faculty of Science > School of Chemistry
Depositing User: Rachel Smith
Date Deposited: 18 Jul 2011 12:20
Last Modified: 21 Sep 2020 23:30
URI: https://ueaeprints.uea.ac.uk/id/eprint/33900
DOI: 10.1074/jbc.M700825200

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