2B3R

Crystal structure of the C2 domain of class II phosphatidylinositide 3-kinase C2

Summary for 2B3R

• Entry DOI: 10.2210/pdb2b3r/pdb
• Descriptor: Phosphatidylinositol-4-phosphate 3-kinase C2 domain-containing alpha polypeptide, SULFATE ION (3 entities in total)
• Functional Keywords: c2 domain, lipid binding, pi3-kinase, transferase
• Biological source: Mus musculus (house mouse)
• Cellular location: Cell membrane: Q61194
• Total number of polymer chains: 2
• Total formula weight: 31499.82

Authors

Liu, L.,Song, X.,He, D.,Komma, C.,Kita, A.,Verbasius, J.V.,Bellamy, H.,Miki, K.,Czech, M.P.,Zhou, G.W. (deposition date: 2005-09-20, release date: 2005-12-13, Last modification date: 2024-02-14)

Primary citation

Liu, L.,Song, X.,He, D.,Komma, C.,Kita, A.,Virbasius, J.V.,Huang, G.,Bellamy, H.D.,Miki, K.,Czech, M.P.,Zhou, G.W.
Crystal structure of the C2 domain of class II phosphatidylinositide 3-kinase C2alpha.
J.Biol.Chem., 281:4254-4260, 2006

PubMed 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.

PubMed: 16338929
DOI: 10.1074/jbc.M510791200

Experimental method

X-RAY DIFFRACTION (2.3 Å)