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Basic Characteristics of Mutations
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Mutation Site
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D150A |
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Mutation Site Sentence
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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 NFkappaB activation, supporting the key role of the fifth transmembrane helix in constitutive activation of signaling by this oncoprotein. |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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LMP-1 |
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Standardized Encoding Gene
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LMP-1
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Genotype/Subtype
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- |
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Viral Reference
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-
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Functional Impact and Mechanisms
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Disease
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-
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Immune
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- |
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Target Gene
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NFKB1
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Clinical and Epidemiological Correlations
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Clinical Information
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- |
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Treatment
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- |
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Location
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- |
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Literature Information
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PMID
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21560118
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Title
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Transmembrane peptides used to investigate the homo-oligomeric interface and binding hotspot of latent membrane protein 1
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Author
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Sammond DW,Joce C,Takeshita R,McQuate SE,Ghosh N,Martin JM,Yin H
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Journal
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Biopolymers
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Journal Info
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2011 Nov;95(11):772-84
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Abstract
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Epstein-Barr virus (EBV), a human gamma-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 NFkappaB activation, supporting the key role of the fifth transmembrane helix in constitutive activation of signaling by this oncoprotein.
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Sequence Data
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-
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