J. Lipid Res. Did you know there is a large type edition? Click here.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

A more recent version of this article appeared on June 1, 2005

Papers In Press, published online ahead of print April 1, 2005
J. Lipid Res., doi:10.1194/jlr.M400401-JLR200
This Article
Right arrow Full Text (Accepted Manuscript)
Right arrow All Versions of this Article:
M400401-JLR200v1
46/6/1303    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 Zhu, X.
Right arrow Articles by Chen, B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zhu, X.
Right arrow Articles by Chen, B.
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 October 12, 2004
Revised on March 4, 2005
Accepted on March 23, 2005

Cysteine mutants of human apolipoprotein A-I: A study on secondary structural and functional properties

Xuewei Zhu, Gang Wu, Wuwei Zeng, Hong Xue, and Baosheng Chen

Department of Biochemistry and Molecular Biology, Chinese Academy of Medical Sciences, Beijing 100005

Corresponding Author: bschen{at}ibms.pumc.edu.cn

ApolipoproteinA-IMilano (apoA-IM) (R173C), a natural mutant of human apoA-I, could protect its carriers against vascular disease. To penetrate the structure and biological activities of cysteine mutants, we generated apoA-IM (R173C) and 5 other cysteine variants of apoA-I at residues 52(S52C), 74(N74C), 107(K107C), 129(G129C) and 195(K195C) by site-directed mutagenesis. Cysteine residues were incorporated in each of the various helical domains at the same helical wheel position as for the substitution in apoA-IM. The secondary structural properties of the monomeric mutants, their capabilities to bind lipid, to promote cholesterol efflux from THP-1 macrophages, and the possibility of anti-peroxidation against lipoxygenase were investigated, respectively. Results showed that the a helical contents of all the cysteine mutants were similar to that of wild-type apoA-I(wtapoA-I). A-IM (R173C) exhibited a weakening structural stability, whereas A-I(G129C) a more stable structure than wtapoA-I as determined by free energy of unfolding. A-I(G129C) and A-I(K195C) exhibited significantly impaired capabilities to bind lipid compared to wtapoA-I. A-I(K107C) possessed a higher capacity to promote the cholesterol efflux from THP-1 macrophages than wtapoA-I, whereas A-IM (R173C) and A-I(K195C) exhibited an impaired efflux capability. Neither A-IM (R173C) nor any other cysteine mutant could resist oxidation against lipoxygenase in our study. In summary, in spite of the similar mutant position on the helix, these variants exhibited different features in structure or biological activities, suggesting the potential influence of the local environment of mutations on the whole polypeptide chain.


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
 J. Lipid Res.Home page
Y. Wang, X. Zhu, G. Wu, L. Shen, and B. Chen
Effect of lipid-bound apoA-I cysteine mutants on lipopolysaccharide-induced endotoxemia in mice
J. Lipid Res., August 1, 2008; 49(8): 1640 - 1645.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
C. Grunfeld and K. R. Feingold
HDL and innate immunity: a tale of two apolipoproteins
J. Lipid Res., August 1, 2008; 49(8): 1605 - 1606.
[Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Ye, X. Wu, L. Wei, D. Tang, P. Sun, M. Bartlam, and Z. Rao
An Insight into the Mechanism of Human Cysteine Dioxygenase: KEY ROLES OF THE THIOETHER-BONDED TYROSINE-CYSTEINE COFACTOR
J. Biol. Chem., February 2, 2007; 282(5): 3391 - 3402.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
 All ASBMB Journals   Journal of Biological Chemistry 
 Molecular and Cellular Proteomics   ASBMB Today 
Copyright © 2005 by the American Society for Biochemistry and Molecular Biology.