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2a01

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'''Crystal Structure of Lipid-free Human Apolipoprotein A-I'''
'''Crystal Structure of Lipid-free Human Apolipoprotein A-I'''
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[[Category: Mishra, V K.]]
[[Category: Mishra, V K.]]
[[Category: Murthy, K H.M.]]
[[Category: Murthy, K H.M.]]
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[[Category: four-helix bundle]]
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[[Category: Four-helix bundle]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 18:26:25 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:46:05 2008''
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Revision as of 15:26, 3 May 2008

Template:STRUCTURE 2a01

Crystal Structure of Lipid-free Human Apolipoprotein A-I


Overview

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.

About this Structure

2A01 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Crystal structure of human apolipoprotein A-I: insights into its protective effect against cardiovascular diseases., Ajees AA, Anantharamaiah GM, Mishra VK, Hussain MM, Murthy HM, Proc Natl Acad Sci U S A. 2006 Feb 14;103(7):2126-31. Epub 2006 Feb 1. PMID:16452169 Page seeded by OCA on Sat May 3 18:26:25 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA, Eric Martz

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