近日，Genes&Development杂志报道，研究者首次解析了磷酸化的Rb蛋白结构，揭示了它失活的机制。
细胞周期蛋白依赖激酶（Cdk）磷酸化视网膜神经胶质瘤蛋白（Rb）通过抑制Rb与E2F转录因子及其他调节蛋白形成复合体来驱动细胞增殖。
研究发现，Rb 608位丝氨酸的磷酸化造成一个弹性的口袋状结构域环。该机构模拟并直接阻断E2F反式激活域(E2FTD)的结合。373位苏氨酸的磷酸化诱导广泛的口袋结构和N末端结构域（RbN）的构象改变。这个首次揭示的多结构域Rb结构证实，RbN在变构抑制E2FTD-口袋结构域结合以及蛋白与口袋结构域特异位点的结合过程中发挥独特的作用。
总之，磷酸化的Rb蛋白结构的破解为该经典生长-抑制复合体的调节机制提供了详细信息，并为了解多位点Cdk磷酸化如何诱导多结构改变，进而影响细胞周期信号通路提供了新的范例。（生物谷Bioon.com)
doi:10.1016/j.cell.2011.10.017
Structures of inactive retinoblastoma protein reveal multiple mechanisms for cell cycle control
Jason R. Burke1, Greg L. Hura2 and Seth M. Rubin1,3
Cyclin-dependent kinase (Cdk) phosphorylation of the Retinoblastoma protein (Rb) drives cell proliferation through inhibition of Rb complexes with E2F transcription factors and other regulatory proteins. We present the first structures of phosphorylated Rb that reveal the mechanism of its inactivation. S608 phosphorylation orders a flexible “pocket” domain loop such that it mimics and directly blocks E2F transactivation domain (E2FTD) binding. T373 phosphorylation induces a global conformational change that associates the pocket and N-terminal domains (RbN). This first multidomain Rb structure demonstrates a novel role for RbN in allosterically inhibiting the E2FTD–pocket association and protein binding to the pocket “LxCxE” site. Together, these structures detail the regulatory mechanism for a canonical growth-repressive complex and provide a novel example of how multisite Cdk phosphorylation induces diverse structural changes to influence cell cycle signaling.
