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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
7
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pubmed:dateCreated |
2006-2-15
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pubmed:databankReference |
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pubmed:abstractText |
Despite three decades of extensive studies on human apolipoprotein A-I (apoA-I), the major protein component in high-density lipoproteins, the molecular basis for its antiatherogenic function is elusive, in part because of lack of a structure of the full-length protein. We describe here the crystal structure of lipid-free apoA-I at 2.4 A. The structure shows that apoA-I is comprised of an N-terminal four-helix bundle and two C-terminal helices. The N-terminal domain plays a prominent role in maintaining its lipid-free conformation, indicating that mutants with truncations in this region form inadequate models for explaining functional properties of apoA-I. A model for transformation of the lipid-free conformation to the high-density lipoprotein-bound form follows from an analysis of solvent-accessible hydrophobic patches on the surface of the structure and their proximity to the hydrophobic core of the four-helix bundle. The crystal structure of human apoA-I displays a hitherto-unobserved array of positively and negatively charged areas on the surface. Positioning of the charged surface patches relative to hydrophobic regions near the C terminus of the protein offers insights into its interaction with cell-surface components of the reverse cholesterol transport pathway and antiatherogenic properties of this protein. This structure provides a much-needed structural template for exploration of molecular mechanisms by which human apoA-I ameliorates atherosclerosis and inflammatory diseases.
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0027-8424
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
14
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pubmed:volume |
103
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2126-31
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
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pubmed:year |
2006
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pubmed:articleTitle |
Crystal structure of human apolipoprotein A-I: insights into its protective effect against cardiovascular diseases.
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pubmed:affiliation |
Center for Biophysical Sciences and Engineering and Atherosclerosis Research Unit and Department of Medicine, University of Alabama, 1530 3rd Avenue South, Birmingham, AL 35294, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, N.I.H., Extramural
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