Transmembrane peptides used to investigate the homo‐oligomeric interface and binding hotspot of latent membrane protein 1
- 10 May 2011
- journal article
- research article
- Published by Wiley in Peptide Science
- Vol. 95 (11), 772-784
- https://doi.org/10.1002/bip.21672
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.Keywords
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