2A01: Crystal Structure Of Lipid-free Human Apolipoprotein A-i

Citation:
Abstract
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.
PDB ID: 2A01Download
MMDB ID: 37495
PDB Deposition Date: 2005/6/15
Updated in MMDB: 2017/11
Experimental Method:
x-ray diffraction
Resolution: 2.4  Å
Source Organism:

*This structure record is obsolete.

Molecular Components in 2A01
Label Count Molecule
Proteins (3 molecules)
3
Apolipoprotein A-I
Molecule annotation
Chemicals (7 molecules)
1
7
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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