title: Crystal structure of C-terminal truncated apolipoprotein A-I reveals the assembly of high density lipoprotein (HDL) by dimerization.
abstract: Apolipoprotein A-I (apoA-I) plays important structural and functional roles in plasma high density lipoprotein (HDL) that is responsible for reverse cholesterol transport. However, a molecular understanding of HDL assembly and function remains enigmatic. The 2.2-Å crystal structure of Δ(185-243)apoA-I reported here shows that it forms a half-circle dimer. The backbone of the dimer consists of two elongated antiparallel proline-kinked helices (five AB tandem repeats). The N-terminal domain of each molecule forms a four-helix bundle with the helical C-terminal region of the symmetry-related partner. The central region forms a flexible domain with two antiparallel helices connecting the bundles at each end. The two-domain dimer structure based on helical repeats suggests the role of apoA-I in the formation of discoidal HDL particles. Furthermore, the structure suggests the possible interaction with lecithin-cholesterol acyltransferase and may shed light on the molecular details of the effect of the Milano, Paris, and Fin mutations.
authors.affiliation: Department of Physiology and Biophysics, Boston University School of Medicine, Boston, Massachusetts 02118.
authors.forename: Xiaohu
authors.initials: X
authors.lastname: Mei
authors.affiliation: Department of Physiology and Biophysics, Boston University School of Medicine, Boston, Massachusetts 02118. Electronic address: atkinson@bu.edu.
authors.forename: David
authors.initials: D
authors.lastname: Atkinson
mesh_terms: D016632:Apolipoprotein A-I / Q000737:chemistry*; D050197:Atherosclerosis / Q000378:metabolism; D002784:Cholesterol / Q000737:chemistry; D003460:Crystallization; D018360:Crystallography, X-Ray / Q000379:methods; D019281:Dimerization; D006801:Humans; D054709:Lecithins / Q000737:chemistry; D008075:Lipoproteins, HDL / Q000737:chemistry*; D009154:Mutation; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000737:chemistry; D017434:Protein Structure, Tertiary; D012492:Salts / Q000737:chemistry; D013499:Surface Properties
chemical_list: D016632:Apolipoprotein A-I; D054709:Lecithins; D008075:Lipoproteins, HDL; D012492:Salts; D002784:Cholesterol; D007862:Phosphatidylcholine-Sterol O-Acyltransferase