2a01

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spinqualitylabelsall models 2a01, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Crystal Structure of Lipid-free Human Apolipoprotein A-I

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

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.

Disease

Known diseases associated with this structure: Amyloidosis, 3 or more types OMIM:[107680], ApoA-I and apoC-III deficiency, combined OMIM:[107680], Corneal clouding, autosomal recessive OMIM:[107680], Hypertriglyceridemia, one form OMIM:[107680], Hypoalphalipoproteinemia OMIM:[107680]

About this Structure

2A01 is a Single protein structure of sequence from Homo sapiens with AC9 as ligand. 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

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