Implications of Membrane Binding by the Fe-S Cluster-Containing N-Terminal Domain in the Mitochondrial Replicative DNA Helicase

Authors

Minyoung So, Department of Biochemistry and Molecular Biology and Center for Mitochondrial Science and Medicine, Michigan State University, East Lansing, MI, United States.
Johnny Stiban, Department of Biochemistry and Molecular Biology and Center for Mitochondrial Science and Medicine, Michigan State University, East Lansing, MI, United States.
Grzegorz L. Ciesielski, Department of Biochemistry and Molecular Biology and Center for Mitochondrial Science and Medicine, Michigan State University, East Lansing, MI, United States.
Stacy L. Hovde, Department of Biochemistry and Molecular Biology and Center for Mitochondrial Science and Medicine, Michigan State University, East Lansing, MI, United States.
Laurie S. Kaguni, Department of Biochemistry and Molecular Biology and Center for Mitochondrial Science and Medicine, Michigan State University, East Lansing, MI, United States.

Document Type

Article

Publication Date

1-1-2021

Abstract

Recent evidence suggests that iron-sulfur clusters (ISCs) in DNA replicative proteins sense DNA-mediated charge transfer to modulate nuclear DNA replication. In the mitochondrial DNA replisome, only the replicative DNA helicase (mtDNA helicase) from has been shown to contain an ISC in its N-terminal, primase-like domain (NTD). In this report, we confirm the presence of the ISC and demonstrate the importance of a metal cofactor in the structural stability of the mtDNA helicase. Further, we show that the NTD also serves a role in membrane binding. We demonstrate that the NTD binds to asolectin liposomes, which mimic phospholipid membranes, through electrostatic interactions. Notably, membrane binding is more specific with increasing cardiolipin content, which is characteristically high in the mitochondrial inner membrane (MIM). We suggest that the N-terminal domain of the mtDNA helicase interacts with the MIM to recruit mtDNA and initiate mtDNA replication. Furthermore, NUBPL, the known ISC donor for respiratory complex I and a putative donor for mtDNA helicase, was identified as a peripheral membrane protein that is likely to execute membrane-mediated ISC delivery to its target proteins.

Publication Title

Frontiers in genetics

Volume

12

First Page

790521

Digital Object Identifier (DOI)

10.3389/fgene.2021.790521

PubMed ID

34950192

ISSN

1664-8021

Language

eng

Citation Information

So, Minyoung; Stiban, Johnny; Ciesielski, Grzegorz L.; Hovde, Stacy L.; and Kaguni, Laurie S., "Implications of Membrane Binding by the Fe-S Cluster-Containing N-Terminal Domain in the Mitochondrial Replicative DNA Helicase" (2021). UNF Faculty Research and Scholarship. 3277.
https://digitalcommons.unf.edu/unf_faculty_publications/3277