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Crystal structure and allosteric activation of protein kinase C ?II.

ABSTRACT: 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 ?II was determined at 4.0 Å, 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?II was derived from small-angle X-ray scattering. Together, these results show how PKC?II is allosterically regulated in two steps, with the second step defining a novel protein kinase regulatory mechanism.

SUBMITTER: Leonard TA

PROVIDER: S-EPMC3104240 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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Crystal structure and allosteric activation of protein kinase C βII.

Leonard Thomas A TA Różycki Bartosz B Saidi Layla F LF Hummer Gerhard G Hurley James H JH

Cell 20110101 1

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 βII was determined at 4.0 Å, 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 ...[more]

PMID: 21215369

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