Phosphatidylglycerol dependent protein translocation across the Escherichia coli inner membrane is inhibited by the anti‐cancer drug doxorubicin

FEBS Letters

Hikita, Chinami²  Mizushima, Shoji²  de Wolf, Frits A.¹  Staffhorst, Rutger W.H.M.¹  Kruijff, Bende¹  Phoenix, David A.¹ 

[1] Centre for Biomembranes and Lipid Enzymology, University of Utrecht, Utrecht, The Netherlands;Institute of Applied Microbiology, University of Tokyo, Tokyo, Japan

关键词: Protein translocation;    Phosphatidylglycerol;    Signal sequence;   

DOI  :  10.1016/0014-5793(93)81543-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

OmpF-Lpp, a model secretory protein, requires both a positively charged signal sequence and phosphatidylglycerol (PG) for efficient translocation across the E. coli inner membrane. Modification of the signal sequence can, however, remove both these prerequisites for translocation providing OmpF-Lpp mutants which undergo either PG and charge dependent or PG and charge independent translocation. Here we show that positively charged membrane interactive compounds (polylysine & doxorubicin) are able to inhibit PG dependent translocation of the OmpF-Lpp signal sequence mutants but not PG independent translocation. Doxorubicin is also shown to bind more efficiently to liposomes containing increased levels of anionic lipid indicating that in these assays it may be inhibiting translocation by preventing electrostatic interaction between the anionic lipid head group and the positively charged signal sequences.

【 授权许可】

Unknown