title: Resting and active states of the ERK2:HePTP complex.
abstract: 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.
authors: Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, Providence, Rhode Island 02912, USA.
authors: Dana M
authors: DM
authors: Francis
authors: Bartosz
authors: B
authors: Różycki
authors: Antoni
authors: A
authors: Tortajada
authors: Gerhard
authors: G
authors: Hummer
authors: Wolfgang
authors: W
authors: Peti
authors: Rebecca
authors: R
authors: Page
mesh_terms: D019950:Mitogen-Activated Protein Kinase 1 / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry / Q000378:metabolism*; D053838:Scattering, Small Angle; D014961:X-Ray Diffraction
chemical_list: D019950:Mitogen-Activated Protein Kinase 1; D017027:Protein Tyrosine Phosphatases