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

ABSTRACT: Human lipoyl synthase (LIAS) is an enzyme containing two [4Fe-4S] clusters (named FeS_RS and FeS_aux) 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 FeS_RS site 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.

SUBMITTER: Saudino G 

PROVIDER: S-EPMC8991016 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature