J. Lipid Res.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

A more recent version of this article appeared on June 1, 2007

Papers In Press, published online ahead of print March 19, 2007
J. Lipid Res., doi:10.1194/jlr.M700086-JLR200
This Article
Right arrow Full Text (Accepted Manuscript)
Right arrow All Versions of this Article:
M700086-JLR200v1
48/6/1386    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
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 arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Parathath, S.
Right arrow Articles by Connelly, M. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Parathath, S.
Right arrow Articles by Connelly, M. A.
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?

Submitted on February 16, 2007
Accepted on March 19, 2007

Effects of amino acid substitutions at glycine 420 on SR-BI cholesterol transport function

Saj Parathath, Yolanda F. Darlington, Margarita de la Llera-Moya, Denise Drazul-Schrader, David L. Williams, Michael C. Phillips, George H. Rothblat, and Margery A. Connelly

Vascular Research, Johnson & Johnson, PRD, Spring House, PA 19477-0776

Corresponding Author: mconnell{at}prdus.jnj.com

Scavenger receptor BI, SR-BI, facilitates the uptake of high density lipoprotein (HDL) cholesteryl esters (CE) in a two step process involving binding of HDL to its extracellular domain and transfer of HDL core CE to a metabolically active membrane pool where they are subsequently hydrolyzed by a neutral CE hydrolase. Recently we characterized a mutant, G420H, which replaced glycine 420 in the extracellular domain of SR-BI with a histidine residue and had a profound effect on SR-BI function. The G420H mutant receptor exhibited a reduced ability to mediate selective HDL CE uptake and was unable to deliver HDL CE for hydrolysis, despite the fact that it retained the ability to bind HDL. This did not hold true if glycine 420 was replaced with an alanine residue; G420A maintained wild type HDL binding and cholesterol transport activity. In order to further understand the role that glycine 420 plays in SR-BI function and why there was a disparity between replacing glycine 420 with a histidine versus an alanine, we generated a battery of point mutants by substituting glycine 420 with amino acids possessing side chains that were either charged, hydrophobic, polar or bulky and tested the resulting mutants for their ability to support HDL binding, HDL cholesterol transport and delivery for hydrolysis. The results indicated that it is most likely the positive charge on the histidine side chain that disrupts the ability of SR-BI to deliver HDL CE to a metabolic pathway within the cell.


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?


This article has been cited by other articles:


Home page
 Mol. Pharmacol.Home page
B. Elbaz, A. Alperovitch, M. M. Gottesman, C. Kimchi-Sarfaty, and H. Rahamimoff
Modulation of Na+-Ca2+ Exchanger Expression by Immunosuppressive Drugs Is Isoform-Specific
Mol. Pharmacol., April 1, 2008; 73(4): 1254 - 1263.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
 All ASBMB Journals   Journal of Biological Chemistry 
 Molecular and Cellular Proteomics   ASBMB Today 
Copyright © 2007 by the American Society for Biochemistry and Molecular Biology.