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

Citation data:

Biopolymers, ISSN: 0006-3525, Vol: 95, Issue: 11, Page: 772-84

Publication Year:
2011
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Citations 9
Citation Indexes 9
PMID:
21560118
DOI:
10.1002/bip.21672
PMCID:
PMC3192311
Author(s):
Sammond, Deanne W; Joce, Catherine; Takeshita, Ryan; McQuate, Sarah E; Ghosh, Nilanjan; Martin, Jennifer M; Yin, Hang
Publisher(s):
Wiley
Tags:
Biochemistry, Genetics and Molecular Biology; Materials Science; Chemistry
article description
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.