Resting and active states of the ERK2:HePTP complex

Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, Providence, Rhode Island 02912, USA.
Journal of the American Chemical Society (Impact Factor: 12.11). 11/2011; 133(43):17138-41. DOI: 10.1021/ja2075136
Source: PubMed


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.

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Available from: Bartosz Różycki
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    • "To analyze this difference in more detail, we determined the ab initio molecular envelope of the ERK2:STEP resting-state complex (Figure 1C). A Dmax of 95 Å was determined by analysis of the P(r) function, which is ∼15 Å shorter than that of the ERK2:HePTP complex (Figure 2) [16]. Thus, like the p38α:STEP resting-state complex [14], the ERK2:STEP resting-state complex is compact (Figure 2), and suggests that the STEPCAT interacts directly with ERK2. "
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