Stochastic sensing of nanomolar inositol 1,4,5-trisphosphate with an engineered pore

被引:115
作者
Cheley, S [1 ]
Gu, LQ
Bayley, H
机构
[1] Texas A&M Univ, Hlth Sci Ctr, Dept Med Biochem & Genet, College Stn, TX 77843 USA
[2] Texas A&M Univ, Hlth Sci Ctr, Dept Chem, College Stn, TX 77843 USA
来源
CHEMISTRY & BIOLOGY | 2002年 / 9卷 / 07期
基金
美国国家卫生研究院;
关键词
D O I
10.1016/S1074-5521(02)00172-2
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
The introduction of a ring of arginine residues near the constriction in the transmembrane beta barrel of the staphylococcal alpha-hemolysin heptamer yielded a pore that could be almost completely blocked by phosphate anions at pH 7.5. Block did not occur with other oxyanions, including nitrate, sulfate, perchlorate, and citrate. Based on this finding, additional pores were engineered with high affinities for important cell signaling molecules, such as the Ca2+-mobilizing second messenger inositol 1,4,5-trisphosphate (IP3), that contain phosphate groups. One of these engineered pores, PRR-2, provides a ring of fourteen arginines that project into the lumen of the transmembrane barrel. Remarkably, PRR-2 bound IP3 with low nanomolar affinity while failing to bind another second messenger, adenosine 3',5'-cyclic monophosphate (cAMP). The engineered alpha-hemolysin pores may be useful as components of stochastic sensors for cell signaling molecules.
引用
收藏
页码:829 / 838
页数:10
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