Structural characterization by computer experiments of the lipid-free LDL-receptor-binding domain of apolipoprotein E

Martine Prévost, Jean-Pierre Kocher

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The structure and dynamics of the lipid-free LDL-receptor-binding domain of apolipoprotein E (apoE-RBD) has been investigated by Molecular Dynamics Simulations. ApoE-RBD in its monomeric lipid-free form is a singular four-helix bundle made up of four elongated amphipathic helices. Analysis of one 1.5 ns molecular dynamics trajectory of apoE-RBD performed in water indicates that the lipid-free domain adopts a structure that exhibits characteristics found in native proteins: it has very stable helices and presents a compact structure. Yet its interior exhibits a larger number of transient atomic-size cavities relative to that found in other proteins of similar size and its apolar side chains are more mobile. The latter features distinguish the elongated four-helix bundle as a slightly disordered structure, which shows a structural likeness with some de novo designed four-helix bundle proteins and shares with the latter a leucine-rich residue composition. We anticipate that these unique properties compared with other native helix bundles may be related to the postulated ability of apoE-RBD to undergo an opening of its bundle upon interaction with phospholipids. The distribution of empty cavities computed along the trajectory in the interface regions between the different pairs of helices reveals that the tertiary contacts in one of the interfaces are weaker suggesting that this particular interface could be more easily ruptured upon lipid association.

Original languageEnglish (US)
Pages (from-to)475-483
Number of pages9
JournalProtein Engineering
Volume12
Issue number6
StatePublished - 1999
Externally publishedYes

Fingerprint

LDL Receptors
Apolipoproteins E
Lipids
Proteins
Molecular dynamics
Molecular Dynamics Simulation
Experiments
Trajectories
Phospholipids
Leucine
Association reactions
Apolipoproteins
Computer simulation
Chemical analysis
Water

Keywords

  • apoE-RBD/LDL-receptor binding domain
  • Four-helix bundle
  • Molecular dynamics
  • Protein packing

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry

Cite this

Structural characterization by computer experiments of the lipid-free LDL-receptor-binding domain of apolipoprotein E. / Prévost, Martine; Kocher, Jean-Pierre.

In: Protein Engineering, Vol. 12, No. 6, 1999, p. 475-483.

Research output: Contribution to journalArticle

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