Deanne W. Sammond and Catherine Joce contributed equally to this work.
1097-0282/asset/BIP_left.gif?v=1&s=f807857598ff440ee8acab64bad01b412bcbb591)
Research Article
Transmembrane peptides used to investigate the homo-oligomeric interface and binding hotspot of latent membrane protein 1†
Article first published online: 10 MAY 2011
DOI: 10.1002/bip.21672
Copyright © 2011 Wiley Periodicals, Inc.
Additional Information
How to Cite
Sammond, D. W., Joce, C., Takeshita, R., McQuate, S. E., Ghosh, N., Martin, J. M. and Yin, H. (2011), Transmembrane peptides used to investigate the homo-oligomeric interface and binding hotspot of latent membrane protein 1. Biopolymers, 95: 772–784. doi: 10.1002/bip.21672
- †
This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Publication History
- Issue published online: 26 AUG 2011
- Article first published online: 10 MAY 2011
- Manuscript Accepted: 29 APR 2011
- Manuscript Revised: 15 FEB 2011
- Manuscript Received: 21 DEC 2010
Funded by
- National Institutes of Health. Grant Number: 1R21CA138373
- National Science Foundation. Grant Number: 0954819
- Cancer League of Colorado
Keywords:
- membrane proteins;
- NF-kappa B;
- peptide chemical synthesis;
- protein–protein interactions;
- CD40;
- Epstein-Barr virus
Abstract
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. © 2011 Wiley Periodicals, Inc. Biopolymers 95: 772-784, 2011.