期刊
CELL
卷 144, 期 1, 页码 55-66出版社
CELL PRESS
DOI: 10.1016/j.cell.2010.12.013
关键词
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资金
- NCI [Y1-CO-1020]
- NIGMS [Y1-GM-1104]
- U.S. Department of Energy, Basic Energy Sciences, Office of Science [DE-AC02-06CH11357]
- Department of Energy, Office of Biological and Environmental Research
- National Institutes of Health, National Center for Research Resources
- EMBO
- Marie Curie International Outgoing Fellowship within the 7th European Community Framework Programme
- National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health
Protein kinase C (PKC) isozymes are the paradigmatic effectors of lipid signaling. PKCs translocate to cell membranes and are allosterically activated upon binding of the lipid diacylglycerol to their C1A and C1B domains. The crystal structure of full-length protein kinase C beta II was determined at 4.0 angstrom, revealing the conformation of an unexpected intermediate in the activation pathway. Here, the kinase active site is accessible to substrate, yet the conformation of the active site corresponds to a low-activity state because the ATP-binding side chain of Phe629 of the conserved NFD motif is displaced. The C1B domain clamps the NFD helix in a low-activity conformation, which is reversed upon membrane binding. A low-resolution solution structure of the closed conformation of PKC beta II was derived from small-angle X-ray scattering. Together, these results show how PKC beta II is allosterically regulated in two steps, with the second step defining a novel protein kinase regulatory mechanism.
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