Advertisement
J. Lipid Res.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1194/jlr.M800474-JLR200 on October 9, 2008

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
M800474-JLR200v1
50/3/546    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Francone, O. L.
Right arrow Articles by Kane, C. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Francone, O. L.
Right arrow Articles by Kane, C. D.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Journal of Lipid Research, Vol. 50, 546-555, March 2009
Copyright © 2009 by American Society for Biochemistry and Molecular Biology

The hydrophobic tunnel present in LOX-1 is essential for oxidized LDL recognition and binding

Omar L. Francone1, Meihua Tu, Lori J. Royer, Jian Zhu, Kimberly Stevens, Joseph J. Oleynek, Zhiwu Lin, Lorraine Shelley, Thomas Sand, Yi Luo and Christopher D. Kane

Department of Atherosclerosis Biology, Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340

Published, JLR Papers in Press, October 9, 2008.

1 To whom correspondence should be addressed. e-mail: omar.l.francone{at}pfizer.com

Lectin-like oxidized LDL (ox-LDL) receptor-1 (LOX-1) is a type-II transmembrane protein that belongs to the C-type lectin family of molecules. LOX-1 acts as a cell surface endocytosis receptor and mediates the recognition and internalization of ox-LDL by vascular endothelial cells. Internalization of ox-LDL by LOX-1 results in a number of pro-atherogenic cellular responses implicated in the development and progression of atherosclerosis. In an effort to elucidate the functional domains responsible for the binding of ox-LDL to the receptor, a series of site-directed mutants were designed using computer modeling and X-ray crystallography to study the functional role of the hydrophobic tunnel present in the LOX-1 receptor. The isoleucine residue (I149) sitting at the gate of the channel was replaced by phenylalanine, tyrosine, or glutamic acid to occlude the channel opening and restrict the docking of ligands to test its functional role in the binding of ox-LDL. The synthesis, intracellular processing, and cellular distribution of all mutants were identical to those of wild type, whereas there was a marked decrease in the ability of the mutants to bind ox-LDL. These studies suggest that the central hydrophobic tunnel that extends through the entire LOX-1 molecule is a key functional domain of the receptor and is critical for the recognition of modified LDL.

Supplementary key words lipoprotein oxidation • scavenger • receptors • endothelial cells

Abbreviations: CHO, Chinese hamster ovary; CTLD, C-terminal C-type lectin-like domain; LOX-1, lectin-like oxidized LDL receptor-1; MSD, Meso Scale Discovery; ox-HDL, oxidized HDL; TBARS, thiobarbituric acid-reactive substances


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Journal of Biological Chemistry 
 Molecular and Cellular Proteomics   ASBMB Today 
Copyright © 2009 by the American Society for Biochemistry and Molecular Biology.
Advertisement
spacer
Advertisement
Advertisement