Crystal Structure of the C2 Domain of Class Ii Phosphatidylinositide 3-kinase C2alpha.
From: Department of Biological Sciences, Louisiana State University, Baton Rouge, 70803, USA.
The Journal of biological chemistry
- Publish Date: Feb 2006
- ISSN: 0021-9258
- Volume: 281
- Issue: 7
- Pages: 4254-60
- Medium: Print
- Language: English
- Citation (JAMA): Liu Lijun, Song Xi, He Dandan, et al. Crystal Structure of the C2 Domain of Class Ii Phosphatidylinositide 3-kinase C2alpha.. J. Biol. Chem. Feb 2006;281:4254-60
Abstract
Phosphatidylinositide (PtdIns) 3-kinase catalyzes the addition of a phosphate group to the 3’-position of phosphatidyl inositol. Accumulated evidence shows that PtdIns 3-kinase can provide a critical signal for cell proliferation, cell survival, membrane trafficking, glucose transport, and membrane ruffling. Mammalian PtdIns 3-kinases are divided into three classes based on structure and substrate specificity. A unique characteristic of class II PtdIns 3-kinases is the presence of both a phox homolog domain and a C2 domain at the C terminus. The biological function of the C2 domain of the class II PtdIns 3-kinases remains to be determined. We have determined the crystal structure of the mCPK-C2 domain, which is the first three-dimensional structural model of a C2 domain of class II PtdIns 3-kinases. Structural studies reveal that the mCPK-C2 domain has a typical anti-parallel beta-sandwich fold. Scrutiny of the surface of this C2 domain has identified three small, shallow sulfate-binding sites. On the basis of the structural features of these sulfate-binding sites, we have studied the lipid binding properties of the mCPK-C2 domain by site-directed mutagenesis. Our results show that this C2 domain binds specifically to PtdIns(3,4)P(2) and PtdIns(4,5)P(2) and that three lysine residues at SBS I site, Lys-1420, Lys-1432, and Lys-1434, are responsible for the phospholipid binding affinity.
Mesh Headings (Keywords): 1-Phosphatidylinositol 3-Kinase, Amino Acid Sequence, Animals, Binding Sites, Crystallization, Dimerization, Mice, Molecular Sequence Data, Phospholipids, Protein Structure, Tertiary
Check for Full Text / PubMed Unique Identifier (PMID): 16338929
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