TY - JOUR
T1 - The third conformation of p38α MAP kinase observed in phosphorylated p38α and in solution
AU - Akella, Radha
AU - Min, Xiaoshan
AU - Wu, Qiong
AU - Gardner, Kevin H.
AU - Goldsmith, Elizabeth J.
N1 - Funding Information:
We thank Mischa Machius, Diana Tomchick, and Chad Brautigam as well as the staff at Argonne National Laboratory for help with Synchrotron data collection. This research was supported by NIH grant DK46993 and grant I1128 from the Robert A. Welch Foundation. Use of the Argonne National Laboratory Structural Biology Center beamlines at the Advanced Photon Source was supported by the U. S. Department of Energy, Office of Biological and Environmental Research, under Contract No. W-31-109-ENG-38.
PY - 2010/12/8
Y1 - 2010/12/8
N2 - MAPKs engage substrates, MAP2Ks, and phosphatases via a docking groove in the C-terminal domain of the kinase. Prior crystallographic studies on the unphosphorylated MAPKs p38α and ERK2 defined the docking groove and revealed long-range conformational changes affecting the activation loop and active site of the kinase induced by peptide. Solution NMR data presented here for unphosphorylated p38α with a MEK3b-derived peptide (p38α/pepMEK3b) validate these findings. Crystallograhic data from doubly phosphorylated active p38α (p38α/TGY/pepMEK3b) reveal a structure similar to unphosphorylated p38α/MEK3b, and distinct from phosphorylated p38γ (p38γ/TGY) and ERK2 (ERK2/TEY). The structure supports the idea that MAP kinases adopt three distinct conformations: unphosphorylated, phosphorylated, and a docking peptide-induced form.
AB - MAPKs engage substrates, MAP2Ks, and phosphatases via a docking groove in the C-terminal domain of the kinase. Prior crystallographic studies on the unphosphorylated MAPKs p38α and ERK2 defined the docking groove and revealed long-range conformational changes affecting the activation loop and active site of the kinase induced by peptide. Solution NMR data presented here for unphosphorylated p38α with a MEK3b-derived peptide (p38α/pepMEK3b) validate these findings. Crystallograhic data from doubly phosphorylated active p38α (p38α/TGY/pepMEK3b) reveal a structure similar to unphosphorylated p38α/MEK3b, and distinct from phosphorylated p38γ (p38γ/TGY) and ERK2 (ERK2/TEY). The structure supports the idea that MAP kinases adopt three distinct conformations: unphosphorylated, phosphorylated, and a docking peptide-induced form.
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U2 - 10.1016/j.str.2010.09.015
DO - 10.1016/j.str.2010.09.015
M3 - Article
C2 - 21134636
AN - SCOPUS:78649775811
SN - 0969-2126
VL - 18
SP - 1571
EP - 1578
JO - Structure
JF - Structure
IS - 12
ER -