Cen Osman, Longnecker Richard
Department of Microbiology and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Curr Top Microbiol Immunol. 2015;391:151-80. doi: 10.1007/978-3-319-22834-1_5.
LMP2A is an EBV-encoded protein with three domains: (a) an N-terminal cytoplasmic domain, which has PY motifs that bind to WW domain-containing E3 ubiquitin ligases and an ITAM that binds to SH2 domain-containing proteins, (b) a transmembrane domain with 12 transmembrane segments that localizes LMP2A in cellular membranes, and (c) a 27-amino acid C-terminal domain which mediates homodimerization and heterodimerization of LMP2 protein isoforms. The most prominent two isoforms of the protein are LMP2A and LMP2B. The LMP2B isoform lacks the 19-amino acid N-terminal domain found in LMP2A, which modulates cellular signaling resulting in a baseline activation of B cells and degradation of cellular kinases leading to the downregulation of normal B cell signaling pathways. These two seemingly contradictory processes allow EBV to establish and maintain latency. LMP2 is expressed in many EBV-associated malignancies. While its antigenic properties may be useful in developing LMP2-specific immunity, the LMP2A N-terminal motifs also provide a basis to target LMP2A-modulated cellular kinases for the development of treatment strategies.
LMP2A是一种由EB病毒编码的蛋白，具有三个结构域：(a) 一个N端胞质结构域，其具有与含WW结构域的E3泛素连接酶结合的PY基序以及与含SH2结构域的蛋白结合的免疫受体酪氨酸激活基序（ITAM）；(b) 一个具有12个跨膜片段的跨膜结构域，将LMP2A定位在细胞膜中；(c) 一个27个氨基酸的C端结构域，介导LMP2蛋白异构体的同二聚化和异二聚化。该蛋白最主要的两种异构体是LMP2A和LMP2B。LMP2B异构体缺少LMP2A中发现的19个氨基酸的N端结构域，该结构域调节细胞信号传导，导致B细胞的基线激活以及细胞激酶的降解，从而导致正常B细胞信号通路的下调。这两个看似矛盾的过程使EB病毒能够建立并维持潜伏状态。LMP2在许多EB病毒相关的恶性肿瘤中表达。虽然其抗原特性可能有助于发展针对LMP2的特异性免疫，但LMP2A的N端基序也为靶向LMP2A调节的细胞激酶以开发治疗策略提供了基础。
