Crystal structure of truncated human apolipoprotein A-I suggests a lipid-bound conformation.
The structure of truncated human apolipoprotein A-I (apo A-I), the major protein component of high density lipoprotein, has been determined at 4-A resolution. The crystals comprise residues 44-243 (exon 4) of apo A-I, a fragment that binds to lipid similarly to intact apo A-I and that retains the lipid-bound conformation even in the absence of lipid. The molecule consists almost entirely of a pseudo-continuous, amphipathic alpha-helix that is punctuated by kinks at regularly spaced proline residues; it adopts a shape similar to a horseshoe of dimensions 125 x 80 x 40 A. Four molecules in the asymmetric unit associate via their hydrophobic faces to form an antiparallel four-helix bundle with an elliptical ring shape. Based on this structure, we propose a model for the structure of apo A-I bound to high density lipoprotein.
Borhani
D W
DW
Department of Organic Chemistry, Southern Research Institute, Birmingham, AL 35205, USA. borhani@sri.org
Rogers
D P
DP
Engler
J A
JA
Brouillette
C G
CG
D000595:Amino Acid Sequence; D016632:Apolipoprotein A-I / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D018360:Crystallography, X-Ray; D006801:Humans; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation
D016632:Apolipoprotein A-I; D008055:Lipids