Structure of concatenated HAMP domains provides a mechanism for signal transduction.

Structure of concatenated HAMP domains provides a mechanism for signal transduction.
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DOI:
10.1016/j.str.2010.01.013
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发表时间:
2010-03-14
期刊:
Structure (London, England : 1993)
影响因子:
--
通讯作者:
Crane BR
Crane BR
中科院分区:
其他
文献类型:
--
作者:
Airola MV;Watts KJ;Bilwes AM;Crane BR

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HAMP 结构域是广泛存在的原核信号传导模块,在跨膜蛋白和可溶性蛋白中以单结构域或多 HAMP 链的形式存在。来自铜绿假单胞菌可溶性受体 Aer2 的 3 单元聚 HAMP 链的晶体结构定义了不同 HAMP 结构域的通用平行四螺旋束结构。两个连续的结构域整合形成串联的 di-HAMP 结构。三个 HAMP 结构域显示出两种不同的构象,它们的不同之处在于螺旋配准、交叉角和旋转的变化。这些构象由不同的保守残基子集来稳定。传递到 HAMP 的已知信号预计会改变两种构象的相对稳定性以及与下游螺旋连接处的卷曲线圈相位抖动的位置。我们提出这两种构象代表相反的 HAMP 信号状态,并提出了一种信号机制,通过该机制 HAMP 结构域在两种状态之间相互转换,这两种状态沿着多 HAMP 链交替。
HAMP domains are widespread prokaryotic signaling modules found as single domains or poly-HAMP chains in both transmembrane and soluble proteins. The crystal structure of a 3 unit poly-HAMP chain from the P. aeruginosa soluble receptor Aer2 defines a universal parallel four-helix bundle architecture for diverse HAMP domains. Two contiguous domains integrate to form a concatenated di-HAMP structure. The three HAMP domains display two distinct conformations that differ by changes in helical register, crossing angles, and rotation. These conformations are stabilized by different subsets of conserved residues. Known signals delivered to HAMP would be expected to switch the relative stability of the two conformations and the position of a coiled-coil phase stutter at the junction with downstream helices. We propose that the two conformations represent opposing HAMP signaling states and suggest a signaling mechanism whereby HAMP domains interconvert between the two states, which alternate down a poly-HAMP chain.
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