The actinobacterial mce4 locus encodes a steroid transporter

William W. Mohn, Robert Van Der Geize, Gordon R. Stewart, Sachi Okamoto, Jie Liu, Lubbert Dijkhuizen, Lindsay D. Eltis

Research output: Contribution to journalArticlepeer-review

128 Citations (Scopus)

Abstract

Bioinformatic analyses have suggested that Mce proteins in diverse actinobacteria are components of complex ATP-binding cassette transporter systems, comprising more than eight distinct proteins. In Mycobacterium tuberculosis, these proteins are implicated in interactions of this deadly pathogen with its human host. Here, we provide direct evidence that the Mce4 system of Rhodococcus jostii RHA1 is a steroid uptake system. Transcriptional analyses indicate that the system is encoded by an 11-gene operon, up-regulated 4.0-fold during growth on cholesterol versus on pyruvate. Growth of RHA1 on cholesterol and uptake of radiolabeled cholesterol both required expression of genes in the mce4 operon encoding two permeases plus eight additional proteins of unknown function. Cholesterol uptake was ATP-dependent and exhibited Michaelis-Menten kinetics with a Km of 0.6 ± 0.1 μM. This uptake system was also essential for growth of RHA1 on β-sitosterol, 5-α-cholestanol, and 5-α-cholestanone. Bioinformatic analysis revealed that all mce4 loci in sequenced genomes are linked to steroid metabolism genes. Thus, we predict that all Mce4 systems are steroid transporters. The transport function of the Mce4 system is consistent with proposed roles of cholesterol and its metabolism in the pathogenesis of M. tuberculosis.

Original languageEnglish
Pages (from-to)35368-35374
Number of pages7
JournalJournal of Biological Chemistry
Volume283
Issue number51
DOIs
Publication statusPublished - Dec 19 2008

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'The actinobacterial mce4 locus encodes a steroid transporter'. Together they form a unique fingerprint.

Cite this