IRF5公司
交易激励
内部收益率3
磷酸化
转录因子
干扰素调节因子
辅活化剂
细胞生物学
丝氨酸
二聚体
核磷蛋白
化学
蛋白质结构
生物
细胞质
生物化学
核运输
细胞核
基因
有机化学
作者
Weijun Chen,Suvana S. Lam,Hema Srinath,Zhaozhao Jiang,John J. Correia,Celia A. Schiffer,Katherine A. Fitzgerald,Kai Lin,William E. Royer
摘要
Interferon regulatory factors (IRFs) are essential in the innate immune response and other physiological processes. Activation of these proteins in the cytoplasm is triggered by phosphorylation of serine and threonine residues in a C-terminal autoinhibitory region, which stimulates dimerization, transport into the nucleus, assembly with the coactivator CBP/p300 and initiation of transcription. The crystal structure of the transactivation domain of pseudophosphorylated human IRF5 strikingly reveals a dimer in which the bulk of intersubunit interactions involve a highly extended C-terminal region. The corresponding region has previously been shown to block CBP/p300 binding to unphosphorylated IRF3. Mutation of key interface residues supports the observed dimer as the physiologically activated state of IRF5 and IRF3. Thus, phosphorylation is likely to activate IRF5 and other family members by triggering conformational rearrangements that switch the C-terminal segment from an autoinihibitory to a dimerization role.
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