Protein kinase C eta (PKC eta) is one of several PKC isoforms found in humans. It is a novel PKC isoform in that it is activated by diacylglycerol and anionic phospholipids but not calcium. The crystal structure of the PKC eta-C2 domain, which is thought to mediate anionic phospholipid sensing in the protein, was determined at 1.75 angstrom resolution. The structure is similar to that of the PKC epsilon C2 domain but with significant variations at the putative lipid-binding site. Two serine residues within PKC eta were identified in vitro as potential autophosphorylation sites. In the unphosphorylated structure both serines line the putative lipid-binding site and may therefore play a role in the lipid-regulation of the kinase. (c) 2006 Published by Elsevier Inc.