近日,，Genes&Development雜志報道,，研究者首次解析了磷酸化的Rb蛋白結構,，揭示了它失活的機制。
細胞周期蛋白依賴激酶（Cdk）磷酸化視網(wǎng)膜神經(jīng)膠質瘤蛋白（Rb）通過抑制Rb與E2F轉錄因子及其他調節(jié)蛋白形成復合體來驅動細胞增殖,。
研究發(fā)現(xiàn),，Rb 608位絲氨酸的磷酸化造成一個彈性的口袋狀結構域環(huán)。該機構模擬并直接阻斷E2F反式激活域(E2FTD)的結合,。373位蘇氨酸的磷酸化誘導廣泛的口袋結構和N末端結構域（RbN）的構象改變,。這個首次揭示的多結構域Rb結構證實，RbN在變構抑制E2FTD-口袋結構域結合以及蛋白與口袋結構域特異位點的結合過程中發(fā)揮獨特的作用,。
總之，磷酸化的Rb蛋白結構的破解為該經(jīng)典生長-抑制復合體的調節(jié)機制提供了詳細信息,，并為了解多位點Cdk磷酸化如何誘導多結構改變,，進而影響細胞周期信號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.
