Transmembrane peptides used to investigate the homo-oligomeric interface and binding hotspot of latent membrane protein 1

Biopolymers. 2011 Nov;95(11):772-84. doi: 10.1002/bip.21672. Epub 2011 May 10.


Epstein-Barr virus (EBV), a human γ-herpesvirus, establishes lifelong infection by targeting the adaptive immune system of the host through memory B cells. Although normally benign, EBV contributes to lymphoid malignancies and lymphoproliferative syndromes in immunocompromised individuals. The viral oncoprotein latent membrane protein 1 (LMP-1) is essential for B lymphocyte immortalization by EBV. The constitutive signaling activity of LMP-1 is dependent on homo-oligomerization of its six-spanning hydrophobic transmembrane domain (TMD). However, the mechanism driving LMP-1 intermolecular interaction is poorly understood. Here, we show that the fifth transmembrane helix (TM5) of LMP-1 strongly self-associates, forming a homotrimeric complex mediated by a polar residue embedded in the membrane, D150. Replacement of this aspartic acid residue with alanine disrupts TM5 self-association in detergent micelles and bacterial cell membranes. A full-length LMP-1 variant harboring the D150A substitution is deficient in NFκB activation, supporting the key role of the fifth transmembrane helix in constitutive activation of signaling by this oncoprotein.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Binding Sites
  • Biopolymers / metabolism*
  • Blotting, Western
  • Circular Dichroism
  • DNA Primers
  • Electrophoresis, Polyacrylamide Gel
  • Molecular Dynamics Simulation
  • Molecular Sequence Data
  • Peptides / metabolism*
  • Point Mutation
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Ultracentrifugation
  • Viral Matrix Proteins / chemistry
  • Viral Matrix Proteins / genetics
  • Viral Matrix Proteins / metabolism*


  • Biopolymers
  • DNA Primers
  • EBV-associated membrane antigen, Epstein-Barr virus
  • Peptides
  • Viral Matrix Proteins