Crystal structure of the C2 domain of class II phosphatidylinositide 3-kinase C2α

被引:29
作者
Liu, LJ
Song, X
He, DD
Komma, C
Kita, A
Virbasius, JV
Huang, GQ
Bellamy, HD
Miki, K
Czech, MP
Zhou, GW [1 ]
机构
[1] Louisiana State Univ, Dept Sci Biol, Baton Rouge, LA 70803 USA
[2] Kyoto Univ, Grad Sch Sci, Dept Chem, Sakyo Ku, Kyoto 6068502, Japan
[3] Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01605 USA
[4] Louisiana State Univ, Ctr Adv Microstruct & Devices, Baton Rouge, LA 70806 USA
关键词
D O I
10.1074/jbc.M510791200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:4254 / 4260
页数:7
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