An MD simulation of the decoy action of Epstein–Barr virus LMP1 protein mimicking the CD40 interaction with TRAF3

The Epstein–Barr virus (EBV) is associated with a variety of malignancies and chronic active EBV infection is a severe systemic disease associated with high rates of mortality and morbidity. In this paper, the dynamics of the interaction of EBV-expressed latent membrane protein 1 (LMP1) with cellula...

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Bibliographic Details
Published in:Theoretical chemistry accounts 2011-10, Vol.130 (2-3), p.401-410
Main Authors: Chung, Wilfredo Credo, Ishida, Toshimasa
Format: Article
Language:English
Subjects:
Atomic/Molecular Structure and Spectra
Chemistry
Chemistry and Materials Science
Epstein-Barr virus
Infections
Inorganic Chemistry
Molecular dynamics
Organic Chemistry
Physical Chemistry
Proteins
Regular Article
Simulation
Theoretical and Computational Chemistry
Viruses
X ray analysis
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Summary:The Epstein–Barr virus (EBV) is associated with a variety of malignancies and chronic active EBV infection is a severe systemic disease associated with high rates of mortality and morbidity. In this paper, the dynamics of the interaction of EBV-expressed latent membrane protein 1 (LMP1) with cellular signaling intermediate tumor necrosis factor receptor (TNFR)-associated factor 3 (TRAF3) is simulated using standard classical molecular dynamics (MD) protocols. For comparison, the dynamics of the interaction of TRAF3 with CD40, a TNFR mimicked by LMP1 to effect EBV infection is also calculated under similar conditions. Essential dynamics (ED) analysis is carried out to identify important degrees of vibrational freedom that relate to protein function and virus infection. Both the MD simulation and ED analysis reveal novel interactions that help explain the structural decoy action of LMP1 over CD40. These interactions involve the consensus sequence PXQXTXX shared by CD40 and LMP1. In LMP1, we have found novel interaction of Asp 209 with TRAF3 and the interaction is crucial although the adjacent Asp 210 was suggested to be essential by the X-ray analysis. In CD40, it is found that the hairpin formation is not indispensable for the interaction with TRAF3.
ISSN:1432-881X
1432-2234
DOI:10.1007/s00214-011-1006-9