7Z3H

Crystal structure of Iba57 from Chaetomium thermophilum

7Z3H の概要

• エントリーDOI: 10.2210/pdb7z3h/pdb
• 分子名称: Transferase-like protein, CITRIC ACID (3 entities in total)
• 機能のキーワード: 4fe-4s, tetrahydrofolate, protein binding
• 由来する生物種: Chaetomium thermophilum
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 286962.95

構造登録者

Altegoer, F.,Mrusek, D.,Bange, G. (登録日: 2022-03-02, 公開日: 2022-09-21, 最終更新日: 2024-11-13)

主引用文献

Muhlenhoff, U.,Weiler, B.D.,Nadler, F.,Millar, R.,Kothe, I.,Freibert, S.A.,Altegoer, F.,Bange, G.,Lill, R.
The iron-sulfur cluster assembly (ISC) protein Iba57 executes a tetrahydrofolate-independent function in mitochondrial [4Fe-4S] protein maturation.
J.Biol.Chem., 298:102465-102465, 2022

PubMed Abstract: Mitochondria harbor the bacteria-inherited iron-sulfur cluster assembly (ISC) machinery to generate [2Fe-2S; iron-sulfur (Fe-S)] and [4Fe-4S] proteins. In yeast, assembly of [4Fe-4S] proteins specifically involves the ISC proteins Isa1, Isa2, Iba57, Bol3, and Nfu1. Functional defects in their human equivalents cause the multiple mitochondrial dysfunction syndromes, severe disorders with a broad clinical spectrum. The bacterial Iba57 ancestor YgfZ was described to require tetrahydrofolate (THF) for its function in the maturation of selected [4Fe-4S] proteins. Both YgfZ and Iba57 are structurally related to an enzyme family catalyzing THF-dependent one-carbon transfer reactions including GcvT of the glycine cleavage system. On this basis, a universally conserved folate requirement in ISC-dependent [4Fe-4S] protein biogenesis was proposed. To test this idea for mitochondrial Iba57, we performed genetic and biochemical studies in Saccharomyces cerevisiae, and we solved the crystal structure of Iba57 from the thermophilic fungus Chaetomium thermophilum. We provide three lines of evidence for the THF independence of the Iba57-catalyzed [4Fe-4S] protein assembly pathway. First, yeast mutants lacking folate show no defect in mitochondrial [4Fe-4S] protein maturation. Second, the 3D structure of Iba57 lacks many of the side-chain contacts to THF as defined in GcvT, and the THF-binding pocket is constricted. Third, mutations in conserved Iba57 residues that are essential for THF-dependent catalysis in GcvT do not impair Iba57 function in vivo, in contrast to an exchange of the invariant, surface-exposed cysteine residue. We conclude that mitochondrial Iba57, despite structural similarities to both YgfZ and THF-binding proteins, does not utilize folate for its function.

PubMed: 36075292
DOI: 10.1016/j.jbc.2022.102465

実験手法

X-RAY DIFFRACTION (2.4 Å)