The C-terminal domain of apolipoprotein A-I contains a lipid-sensitive conformational trigger

Michael N. Oda, Trudy M. Forte, Robert O. Ryan, John C Voss

Research output: Contribution to journalArticle

109 Citations (Scopus)

Abstract

Exchangeable apolipoproteins can convert between lipid-free and lipid-associated states. The C-terminal domain of human apolipoprotein A-I (apoA-I) plays a role in both lipid binding and self-association. Site-directed spin-label electron paramagnetic resonance spectroscopy was used to examine the structure of the apoA-I C terminus in lipid-free and lipid-associated states. Nitroxide spin-labels positioned at defined locations throughout the C terminus were used to define discrete secondary structural elements. Magnetic interactions between probes localized at positions 163, 217 and 226 in singly and doubly labeled apoA-I gave inter- and intramolecular distance information, providing a basis for mapping apoA-I tertiary and quaternary structure. Spectra of apoA-I in reconstituted HDL revealed a lipid-induced transition of defined random coils and β-strands into α-helices. This conformational switch is analogous to triggered events in viral fusion proteins and may serve as a means to overcome the energy barriers of lipid sequestration, a critical step in cholesterol efflux and HDL assembly.

Original languageEnglish (US)
Pages (from-to)455-460
Number of pages6
JournalNature Structural Biology
Volume10
Issue number6
DOIs
StatePublished - Jun 1 2003

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Apolipoprotein A-I
Lipids
Spin Labels
Viral Fusion Proteins
Apolipoproteins
Energy barriers
Electron Spin Resonance Spectroscopy
HDL Cholesterol
Paramagnetic resonance
Spectrum Analysis
Cholesterol
Switches
Association reactions
Spectroscopy

ASJC Scopus subject areas

  • Biochemistry
  • Structural Biology
  • Genetics

Cite this

The C-terminal domain of apolipoprotein A-I contains a lipid-sensitive conformational trigger. / Oda, Michael N.; Forte, Trudy M.; Ryan, Robert O.; Voss, John C.

In: Nature Structural Biology, Vol. 10, No. 6, 01.06.2003, p. 455-460.

Research output: Contribution to journalArticle

Oda, Michael N. ; Forte, Trudy M. ; Ryan, Robert O. ; Voss, John C. / The C-terminal domain of apolipoprotein A-I contains a lipid-sensitive conformational trigger. In: Nature Structural Biology. 2003 ; Vol. 10, No. 6. pp. 455-460.
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