Department of Microbiology, University of Georgia, Athens, Georgia 30602-2605, USA.
J Biol Chem. 2010 Oct 15;285(42):31923-9. doi: 10.1074/jbc.M110.152447. Epub 2010 Aug 6.
Three multiprotein systems are known for iron-sulfur (Fe-S) cluster biogenesis in prokaryotes and eukaryotes as follows: the NIF (nitrogen fixation), the ISC (iron-sulfur cluster), and the SUF (mobilization of sulfur) systems. In all three, cysteine is the physiological sulfur source, and the sulfur is transferred from cysteine desulfurase through a persulfidic intermediate to a scaffold protein. However, the biochemical nature of the sulfur source for Fe-S cluster assembly in archaea is unknown, and many archaea lack homologs of cysteine desulfurases. Methanococcus maripaludis is a methanogenic archaeon that contains a high amount of protein-bound Fe-S clusters (45 nmol/mg protein). Cysteine in this archaeon is synthesized primarily via the tRNA-dependent SepRS/SepCysS pathway. When a ΔsepS mutant (a cysteine auxotroph) was grown with (34)S-labeled sulfide and unlabeled cysteine, <8% of the cysteine, >92% of the methionine, and >87% of the sulfur in the Fe-S clusters in proteins were labeled, suggesting that the sulfur in methionine and Fe-S clusters was derived predominantly from exogenous sulfide instead of cysteine. Therefore, this investigation challenges the concept that cysteine is always the sulfur source for Fe-S cluster biosynthesis in vivo and suggests that Fe-S clusters are derived from sulfide in those organisms, which live in sulfide-rich habitats.
已知三种多蛋白系统参与原核生物和真核生物的铁硫（Fe-S）簇生物发生：NIF（氮固定）、ISC（铁硫簇）和 SUF（硫动员）系统。在这三种系统中，半胱氨酸是生理硫源，硫通过过硫化物中间体从半胱氨酸脱硫酶转移到支架蛋白上。然而，古菌中 Fe-S 簇组装的硫源的生化性质尚不清楚，并且许多古菌缺乏半胱氨酸脱硫酶的同源物。产甲烷球菌是一种产甲烷古菌，含有大量与蛋白质结合的 Fe-S 簇（45 nmol/mg 蛋白）。该古菌中的半胱氨酸主要通过依赖 tRNA 的 SepRS/SepCysS 途径合成。当生长在 (34)S 标记的硫化物和未标记的半胱氨酸中的 ΔsepS 突变体（半胱氨酸营养缺陷型）时，蛋白质中 Fe-S 簇中的 <8%的半胱氨酸、>92%的蛋氨酸和 >87%的硫被标记，表明蛋氨酸和 Fe-S 簇中的硫主要来自外源性硫化物而不是半胱氨酸。因此，这项研究挑战了半胱氨酸始终是体内 Fe-S 簇生物合成的硫源这一概念，并表明 Fe-S 簇来自生活在富含硫化物环境中的那些生物体中的硫化物。
