Human lipoyl synthase (LIAS) is an enzyme containing two [4Fe-4S] clusters (named FeSRSand FeSaux) involved in the biosynthesis of the lipoyl cofactor. The mechanism by which a [4Fe-4S] cluster is inserted into LIAS has thus far remained elusive. Here we show that NFU1 and ISCA1 of the mitochondrial iron-sulfur cluster assembly machinery, via forming a heterodimeric complex, are the key factors for the insertion of a [4Fe-4S] cluster into the FeSRSsite of LIAS. In this process, the crucial actor is the C-domain of NFU1, which, by exploiting a protein-interaction affinity gradient increasing from ISCA1 to LIAS, drives the cluster to its final destination.

Protein-Interaction Affinity Gradient Drives [4Fe-4S] Cluster Insertion in Human Lipoyl Synthase / Saudino G.; Ciofi-Baffoni S.; Banci L.. - In: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY. - ISSN 0002-7863. - STAMPA. - 144:(2022), pp. 5713-5717. [10.1021/jacs.1c13626]

Protein-Interaction Affinity Gradient Drives [4Fe-4S] Cluster Insertion in Human Lipoyl Synthase

Saudino G.;Ciofi-Baffoni S.
;
Banci L.
2022

Abstract

Human lipoyl synthase (LIAS) is an enzyme containing two [4Fe-4S] clusters (named FeSRSand FeSaux) involved in the biosynthesis of the lipoyl cofactor. The mechanism by which a [4Fe-4S] cluster is inserted into LIAS has thus far remained elusive. Here we show that NFU1 and ISCA1 of the mitochondrial iron-sulfur cluster assembly machinery, via forming a heterodimeric complex, are the key factors for the insertion of a [4Fe-4S] cluster into the FeSRSsite of LIAS. In this process, the crucial actor is the C-domain of NFU1, which, by exploiting a protein-interaction affinity gradient increasing from ISCA1 to LIAS, drives the cluster to its final destination.
2022
144
5713
5717
Saudino G.; Ciofi-Baffoni S.; Banci L.
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1267464
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