Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (3)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Prévost, M.
Right arrow Articles by Kocher, J.-P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Prévost, M.
Right arrow Articles by Kocher, J.-P.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Protein Engineering, Vol. 12, No. 6, 475-483, June 1999
© 1999 Oxford University Press

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

Martine Prévost1 and Jean-Pierre Kocher2

Ingénierie Biomoléculaire, Université Libre de Bruxelles, CP 165/64,Av. F. Roosevelt, B-1050 Bruxelles, Belgium and 2 Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA

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.

Keywords: apoE-RBD/LDL-receptor binding domain/four-helix bundle/Molecular Dynamics/protein packing

1 To whom correspondence should be addressed


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.