The intrinsically disordered Tarp protein from chlamydia binds actin with a partially preformed helix.
The intrinsically disordered Tarp protein from chlamydia binds actin with a partially preformed helix.
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DOI：
10.1038/s41598-018-20290-8
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发表时间：
2018-01-31
影响因子：
4.6
通讯作者：
Blumenschein TMA
中科院分区：
文献类型：
--
作者：
Tolchard J;Walpole SJ;Miles AJ;Maytum R;Eaglen LA;Hackstadt T;Wallace BA;Blumenschein TMA
Tarp（易位肌动蛋白募集磷酸化蛋白）是所有衣原体共有的一种效应蛋白，在感染的初始阶段起重塑宿主肌动蛋白细胞骨架的作用。在沙眼衣原体中，与肌动蛋白单体的直接结合已被广泛定位到一个100个残基的区域（726-825），预计该区域主要是无序的，除了与其他WH2肌动蛋白结合基序同源的约10个残基α-螺旋斑块。生物物理研究表明，Tarp726-825结构体表现为典型的内在无序蛋白；通过核磁共振弛豫测量和化学位移分析，鉴定出10个残基wh2同源区表现出部分α-螺旋结构。在g -肌动蛋白存在的情况下，对同一结构进行等温滴定量热实验表明，结合事件具有良好的定义，化学计量比为1:1，Kd为102 nM，而同步辐射圆二色光谱表明，结合伴随着螺旋二级结构的增加。此外，在g -肌动蛋白存在下的核磁共振实验表明，这种相互作用影响了所提出的wh2样α-螺旋区域，支持了硅对接计算的结果，该结果表明，当折叠时，α-螺旋结合在肌动蛋白疏水性间隙内，与其他肌动蛋白相关蛋白一样。
Tarp (translocated actin recruiting phosphoprotein) is an effector protein common to all chlamydial species that functions to remodel the host-actin cytoskeleton during the initial stage of infection. In C. trachomatis, direct binding to actin monomers has been broadly mapped to a 100-residue region (726–825) which is predicted to be predominantly disordered, with the exception of a ~10-residue α-helical patch homologous to other WH2 actin-binding motifs. Biophysical investigations demonstrate that a Tarp726–825 construct behaves as a typical intrinsically disordered protein; within it, NMR relaxation measurements and chemical shift analysis identify the ten residue WH2-homologous region to exhibit partial α-helix formation. Isothermal titration calorimetry experiments on the same construct in the presence of monomeric G-actin show a well defined binding event with a 1:1 stoichiometry and Kd of 102 nM, whilst synchrotron radiation circular dichroism spectroscopy suggests the binding is concomitant with an increase in helical secondary structure. Furthermore, NMR experiments in the presence of G-actin indicate this interaction affects the proposed WH2-like α-helical region, supporting results from in silico docking calculations which suggest that, when folded, this α-helix binds within the actin hydrophobic cleft as seen for other actin-associated proteins.
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DOI：
10.1073/pnas.0603044103
发表时间：
2006-10-17
影响因子：
11.1
作者：
Jewett, Travis J.;Fischer, Elizabeth R.;Hackstadt, Ted
通讯作者：
Hackstadt, Ted
影响因子：
3.1
作者：
Lutter, Erika I.;Bonner, Christine;Hackstadt, Ted
通讯作者：
Hackstadt, Ted
DOI：
10.1083/jcb.200909095
发表时间：
2010-07-12
期刊：
The Journal of cell biology
影响因子：
--
作者：
Mehlitz A;Banhart S;Mäurer AP;Kaushansky A;Gordus AG;Zielecki J;Macbeath G;Meyer TF
通讯作者：
Meyer TF
影响因子：
3.2
作者：
Jiwani, Shahanawaz;Alvarado, Stephenie;Jewett, Travis J.
通讯作者：
Jewett, Travis J.
影响因子：
2.2
作者：
PALMER, AG;CAVANAGH, J;RANCE, M
通讯作者：
RANCE, M