Oligomeric quaternary structure of Escherichia coli and Mycobacterium smegmatis Lhr helicases is nucleated by a novel C-terminal domain composed of five winged-helix modules Journal Article
| Authors: | Warren, G. M.; Wang, J.; Patel, D. J.; Shuman, S. |
| Article Title: | Oligomeric quaternary structure of Escherichia coli and Mycobacterium smegmatis Lhr helicases is nucleated by a novel C-terminal domain composed of five winged-helix modules |
| Abstract: | Mycobacterium smegmatis Lhr (MsmLhr; 1507-aa) is the founder of a novel clade of bacterial helicases. MsmLhr consists of an N-terminal helicase domain (aa 1-856) with a distinctive tertiary structure (Lhr-Core) and a C-terminal domain (Lhr-CTD) of unknown structure. Here, we report that Escherichia coli Lhr (EcoLhr; 1538-aa) is an ATPase, translocase and ATP-dependent helicase. Like MsmLhr, EcoLhr translocates 3' to 5' on ssDNA and unwinds secondary structures en route, with RNA:DNA hybrid being preferred versus DNA:DNA duplex. The ATPase and translocase activities of EcoLhr inhere to its 877-aa Core domain. Full-length EcoLhr and MsmLhr have homo-oligomeric quaternary structures in solution, whereas their respective Core domains are monomers. The MsmLhr CTD per se is a homo-oligomer in solution. We employed cryo-EM to solve the structure of the CTD of full-length MsmLhr. The CTD protomer is composed of a series of five winged-helix (WH) modules and a β-barrel module. The CTD adopts a unique homo-tetrameric quaternary structure. A Lhr-CTD subdomain, comprising three tandem WH modules and the β-barrel, is structurally homologous to AlkZ, a bacterial DNA glycosylase that recognizes and excises inter-strand DNA crosslinks. This homology is noteworthy given that Lhr is induced in mycobacteria exposed to the inter-strand crosslinker mitomycin C. © The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research. |
| Journal Title: | Nucleic Acids Research |
| Volume: | 49 |
| Issue: | 7 |
| ISSN: | 0305-1048 |
| Publisher: | Oxford University Press |
| Date Published: | 2021-04-19 |
| Start Page: | 3876 |
| End Page: | 3887 |
| Language: | English |
| DOI: | 10.1093/nar/gkab145 |
| PUBMED: | 33744958 |
| PROVIDER: | scopus |
| PMCID: | PMC8053096 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 June 2021 -- Source: Scopus |
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