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PMID: 14500900 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Redefining cholesterol's role in the mechanism of the cholesterol-dependent cytolysins.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 100 ·No. 20 ·2003-09-30 ·Pages 11315-20

Giddings KS, Johnson AE, Tweten RK

Abstract

The cholesterol-dependent cytolysins (CDCs) constitute a large family of pore-forming toxins that function exclusively on cholesterol-containing membranes. A detailed analysis of the various stages in the cytolytic mechanism of three members of the CDC family revealed that significant depletion of cholesterol from the erythrocyte membrane stalls these toxins in the prepore complex. Therefore, the depletion of membrane cholesterol prevents the insertion of the transmembrane beta-barrel and pore formation. These unprecedented findings provide a paradigm for the involvement of cholesterol in the CDC cytolytic mechanism and that of other pore-forming toxins whose activity is enhanced by the presence of membrane cholesterol.

MeSH Terms
Base Sequence Cholesterol/metabolism,physiology Cytotoxins/physiology DNA Primers Membrane Lipids/metabolism Spectrometry, Fluorescence
Chemicals
Cytotoxins DNA Primers Membrane Lipids Cholesterol
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Giddings Kara S
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104.
Johnson Arthur E
Tweten Rodney K
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.2033520100
Published
2003-09-30
Epub
2003-00-19
Pages
11315-20
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC208754
Subset
IM
Grants
NIAID NIH HHS · R01 AI037657 · United States
NIAID NIH HHS · AI37657 · United States
External Links
PubMed source DOI: 10.1073/pnas.2033520100 PMC Full Text View journal details
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