1GMI

Structure of the c2 domain from novel protein kinase C epsilon

Summary for 1GMI

• Entry DOI: 10.2210/pdb1gmi/pdb
• Descriptor: PROTEIN KINASE C, EPSILON TYPE, MAGNESIUM ION (3 entities in total)
• Functional Keywords: kinase, pkc, c2 domain, phospholipids, pkc epsilon.
• Biological source: RATTUS RATTUS (RAT)
• Total number of polymer chains: 1
• Total formula weight: 15222.44

Authors

Ochoa, W.F.,Garcia-Garcia, J.,Fita, I.,Corbalan-Garcia, S.,Verdaguer, N.,Gomez-Fernandez, J.C. (deposition date: 2001-09-14, release date: 2001-10-25, Last modification date: 2024-05-08)

Primary citation

Ochoa, W.F.,Garcia-Garcia, J.,Fita, I.,Corbalan-Garcia, S.,Verdaguer, N.,Gomez-Fernandez, J.C.
Structure of the C2 Domain from Novel Protein Kinase Cepsilon. A Membrane Binding Model for Ca(2+ )-Independent C2 Domains
J.Mol.Biol., 311:837-, 2001

PubMed Abstract: Protein kinase Cepsilon (PKCepsilon) is a member of the novel PKCs which are activated by acidic phospholipids, diacylglycerol and phorbol esters, but lack the calcium dependence of classical PKC isotypes. The crystal structures of the C2 domain of PKCepsilon, crystallized both in the absence and in the presence of the two acidic phospholipids, 1,2-dicaproyl-sn-phosphatidyl-l-serine (DCPS) and 1,2-dicaproyl-sn-phosphatidic acid (DCPA), have now been determined at 2.1, 1.7 and 2.8 A resolution, respectively. The central feature of the PKCepsilon-C2 domain structure is an eight-stranded, antiparallel, beta-sandwich with a type II topology similar to that of the C2 domains from phospholipase C and from novel PKCdelta. Despite the similar topology, important differences are found between the structures of C2 domains from PKCs delta and epsilon, suggesting they be considered as different PKC subclasses. Site-directed mutagenesis experiments and structural changes in the PKCepsilon-C2 domain from crystals with DCPS or DCPA indicate, though phospholipids were not visible in these structures, that loops joining strands beta1-beta2 and beta5-beta6 participate in the binding to anionic membranes. The different behavior in membrane-binding and activation between PKCepsilon and classical PKCs appears to originate in localized structural changes, which include a major reorganization of the region corresponding to the calcium binding pocket in classical PKCs. A mechanism is proposed for the interaction of the PKCepsilon-C2 domain with model membranes that retains basic features of the docking of C2 domains from classical, calcium-dependent, PKCs.

PubMed: 11518534
DOI: 10.1006/JMBI.2001.4910

Experimental method

X-RAY DIFFRACTION (1.7 Å)