Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, Providence, Rhode Island 02912, USA.
J Am Chem Soc. 2011 Nov 2;133(43):17138-41. doi: 10.1021/ja2075136. Epub 2011 Oct 10.
The MAP kinase ERK2 (ERK2, extracellular signal-regulated kinase 2) is regulated by numerous phosphatases that tightly control its activity. For example, the hematopoietic tyrosine phosphatase (HePTP) negatively regulates T cell activation in lymphocytes via ERK2 dephosphorylation. However, only very limited structural information is available for these biologically important complexes. Here, we use small-angle X-ray scattering combined with EROS ensemble refinement to characterize the structures of the resting and active states of ERK2:HePTP complexes. Our data show that the resting state ERK2:HePTP complex adopts a highly extended, dynamic conformation that becomes compact and ordered in the active state complex. This work experimentally demonstrates that these complexes undergo significant dynamic structural changes in solution and provides the first structural insight into an active state MAPK complex.
MAP 激酶 ERK2（ERK2，细胞外信号调节激酶 2）受到许多磷酸酶的调节，这些磷酸酶可严格控制其活性。例如，造血酪氨酸磷酸酶（HePTP）通过 ERK2 去磷酸化负调控淋巴细胞中的 T 细胞活化。然而，对于这些重要的生物复合物，仅有非常有限的结构信息可用。在这里，我们使用小角 X 射线散射结合 EROS 集合精修来表征 ERK2：HePTP 复合物的静息态和激活态结构。我们的数据表明，静息态 ERK2：HePTP 复合物采用高度伸展的动态构象，在激活态复合物中变得紧凑有序。这项工作从实验上证明了这些复合物在溶液中会发生显著的动态结构变化，并首次提供了对活性状态 MAPK 复合物的结构见解。
