The structural basis of cyclic diguanylate signal transduction by PilZ domains
The structural basis of cyclic diguanylate signal transduction by PilZ domains
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DOI：
10.1038/sj.emboj.7601918
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发表时间：
2007-12-12
期刊：
影响因子：
11.4
通讯作者：
Hunt, John F.
中科院分区：
文献类型：
--
作者：
Benach, Jordi;Swaminathan, Swarup S.;Hunt, John F.
在真细菌中，第二信使环二胍酸盐（c-di-GMP）控制着运动生长和无根生长之间的转变，但对感知其浓度的蛋白质知之甚少。生物信息学分析表明，PilZ结构域结合c-二- gmp和变构调节效应途径。我们已经确定了c-di-GMP与VCA0042/PlzD结合的1.9埃晶体结构，VCA0042/PlzD是一种来自霍乱弧菌的含有PilZ结构域的蛋白。霍乱弧菌有效感染小鼠需要这种蛋白或另一种特定的含有PilZ结构域的蛋白。VCA0042/PlzD包括一个c端PilZ结构域和一个具有类似β -桶状褶皱的n端结构域。C-di-GMP与PilZ结构域中9个强保守残基中的7个接触，包括7个残基长n端环中的3个，该环在缠绕C-di-GMP时经历了构象开关。这种开关使PilZ结构域与n端结构域紧密结合，形成一个新的变构相互作用表面，跨越这些结构域和它们的界面处的c-di-GMP。极小的n端构象开关可能解释了PilZ结构域的进化多样化。
The second messenger cyclic diguanylate (c-di-GMP) controls the transition between motile and sessile growth in eubacteria, but little is known about the proteins that sense its concentration. Bioinformatics analyses suggested that PilZ domains bind c-di-GMP and allosterically modulate effector pathways. We have determined a 1.9 angstrom crystal structure of c-di-GMP bound to VCA0042/PlzD, a PilZ domain-containing protein from Vibrio cholerae. Either this protein or another specific PilZ domain-containing protein is required for V. cholerae to efficiently infect mice. VCA0042/PlzD comprises a C-terminal PilZ domain plus an N-terminal domain with a similar beta-barrel fold. C-di-GMP contacts seven of the nine strongly conserved residues in the PilZ domain, including three in a seven-residue long N-terminal loop that undergoes a conformational switch as it wraps around c-di-GMP. This switch brings the PilZ domain into close apposition with the N-terminal domain, forming a new allosteric interaction surface that spans these domains and the c-di-GMP at their interface. The very small size of the N-terminal conformational switch is likely to explain the facile evolutionary diversification of the PilZ domain.