How the lipid-free structure of the N-terminal truncated human apoA-I converts to the lipid-bound form: new insights from NMR and X-ray structural comparison.
The X-ray structure of the N-terminal truncated human apoA-I [Borhani et al., Proc. Natl. Acad. Sci. USA 94 (1997) 12291] and the NMR structure of intact human apoA-I [Okon et al., FEBS Lett. 517 (2002) 139] found similar repeating helices. The crystal structure is a twisted circular four-helix bundle, consisting of four molecules of apoA-I(44-243), where four copies of the lecithin:cholesterol acyltransferase (LCAT)-activating domains are located outside the ring structure, while the aromatic-rich strong lipid-binding domains are inside. This architecture suggests a lipid-binding mechanism that lipids directly enter the hole of the crystal structure. Indeed, four copies of Trp50 and Trp72 are exposed and oriented toward the center of the ring, initiating lipid binding. This is followed by the inside-out rotations of the terminal helices to make a belt with all the hydrophobic faces of the helices facing inward. Such lipid-binding induced rotations have an impact on the conformation of the lipid-free form. Indeed, the structure of residues 78-81 changes from helical (free) to disordered (bound) while the structure of residues 221-227 changes from extended to helical.
Wang
Guangshun
G
Eppley Institute for Cancer Research, 986805 Nebraska Medical Center, University of Nebraska Medical Center, Omaha, NE 68198-6805, USA. gwang@unmc.edu
D016632:Apolipoprotein A-I / Q000737:chemistry / Q000378:metabolism*; D018360:Crystallography, X-Ray; D006801:Humans; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation
D016632:Apolipoprotein A-I; D008055:Lipids