A secreted high-affinity inhibitor of human TNF from Tanapox virus
A secreted high-affinity inhibitor of human TNF from Tanapox virus
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DOI：
10.1073/pnas.0737244100
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发表时间：
2003-04-15
影响因子：
11.1
通讯作者：
McFadden, G
中科院分区：
文献类型：
--
作者：
Brunetti, CR;Paulose-Murphy, M;McFadden, G
一类分泌痘病毒肿瘤坏死因子（TNF）结合蛋白已被分离Tanapox感染的细胞上清液。抑制剂结合到TNF-亲和柱上，并被鉴定为2L基因的产物。对来自其他亚塔痘病毒和猪痘病毒的2L家族成员的序列分析未发现与任何已知细胞基因的序列同源性。表达的Tanapox病毒2L蛋白以高亲和力（Kd = 43 pM）与人TNF结合，并表现出异常缓慢的解离速率。然而，2L不能与广泛的人TNF家族成员结合。2L蛋白可以抑制人TNF与TNF受体I和II的结合，并阻断TNF诱导的细胞溶解。因此，Tanapox病毒2L代表了人TNF的抑制剂，并提供了一种调节TNF活性的独特策略。
A class of secreted poxvirus tumor necrosis factor (TNF)-binding proteins has been isolated from Tanapox-infected cell supernatants. The inhibitor bound to a TNF-affinity column and was identified as the product of the 2L gene. Sequence analysis of 2L family members from other yatapoxviruses and swinepox virus yielded no sequence homology to any known cellular gene. The expressed Tanapox virus 2L protein bound to human TNF with high affinity (K-d = 43 pM) and exhibits an unusually slow off-rate. However, 2L is unable to bind to a wide range of human TNF family members. The 2L protein can inhibit human TNF from binding to TNF receptors I and II as well as block TNF-induced cytolysis. Thus, Tanapox virus 2L represents an inhibitor of human TNF and offers a unique strategy with which to modulate TNF activity.