Transglutaminase-Mediated Cross-Linking of Tropoelastin to Fibrillin Stabilises the Elastin Precursor Prior to Elastic Fibre Assembly.
Transglutaminase-Mediated Cross-Linking of Tropoelastin to Fibrillin Stabilises the Elastin Precursor Prior to Elastic Fibre Assembly.
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在弹性纤维组件之前，透射蛋白酶介导的晶洛未蛋白酶介导的交联使弹性蛋白前体稳定。
DOI：
10.1016/j.jmb.2020.08.023
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发表时间：
2020-10-02
影响因子：
5.6
通讯作者：
Tarakanova A
中科院分区：
文献类型：
--
作者：
Lockhart-Cairns MP;Newandee H;Thomson J;Weiss AS;Baldock C;Tarakanova A
弹性纤维是所有哺乳动物弹性组织（如血管、肺和皮肤）的基本组成部分，并且对于它们赋予的机械性能至关重要。弹性纤维的主要成分是弹性蛋白和弹性蛋白，其中弹性纤维的正确形成需要弹性蛋白微纤维支架用于弹性蛋白的沉积。先前已经证明，弹性蛋白和弹性蛋白原（弹性蛋白前体）之间的相互作用增加弹性蛋白原的组装速率。此外，原弹性蛋白和弹性蛋白可以通过转氨酶-2交联，但交联对它们的弹性性质的作用还有待阐明。在这里，我们表明，转氨酶交联支持形成1：1化学计量的原纤维蛋白-原弹性蛋白复合物。SAXS数据显示，复合物保留了单个蛋白质的特征，但延长了支持端到端组装。构建弹性网络模型，以比较弹性蛋白原和弹性蛋白单独以及在交联复合物中的动力学。进行正常模式分析以确定结构的能量上最有利的、生物学上可接近的运动，这表明在复合物内，原弹性蛋白是较不移动的，并且这种分子稳定化沿着原弹性蛋白分子的长度延伸到远离交联位点的区域。总之，这些数据表明，交联的长期稳定作用是由于Escarin与原弹性蛋白的共价连接而发生的。这项工作提供了深入了解原弹性蛋白和弹性蛋白的相互作用，以及交联形成如何稳定弹性蛋白前体，使其为弹性纤维组装做好准备。哺乳动物组织弹性所必需的弹性纤维含有弹性蛋白和弹性蛋白。组织转氨酶交联弹性蛋白和弹性蛋白原以形成复合物。该复合体具有支持端到端组装的细长结构。交联限制了原弹性蛋白和弹性蛋白的分子运动。稳定化可以为弹性纤维组装提供起始分子机制。
Elastic fibres are essential components of all mammalian elastic tissues such as blood vessels, lung and skin, and are critically important for the mechanical properties they endow. The main components of elastic fibres are elastin and fibrillin, where correct formation of elastic fibres requires a fibrillin microfibril scaffold for the deposition of elastin. It has been demonstrated previously that the interaction between fibrillin and tropoelastin, the elastin precursor, increases the rate of assembly of tropoelastin. Furthermore, tropoelastin and fibrillin can be cross-linked by transglutaminase-2, but the function of cross-linking on their elastic properties is yet to be elucidated. Here we show that transglutaminase cross-linking supports formation of a 1:1 stoichiometric fibrillin–tropoelastin complex. SAXS data show that the complex retains features of the individual proteins but is elongated supporting end-to-end assembly. Elastic network models were constructed to compare the dynamics of tropoelastin and fibrillin individually as well as in the cross-linked complex. Normal mode analysis was performed to determine the structures' most energetically favourable, biologically accessible motions which show that within the complex, tropoelastin is less mobile and this molecular stabilisation extends along the length of the tropoelastin molecule to regions remote from the cross-linking site. Together, these data suggest a long-range stabilising effect of cross-linking that occurs due to the covalent linkage of fibrillin to tropoelastin. This work provides insight into the interactions of tropoelastin and fibrillin and how cross-link formation stabilises the elastin precursor so it is primed for elastic fibre assembly. Elastic fibres, essential for mammalian tissue elasticity, contain elastin and fibrillin. Tissue transglutaminase cross-links fibrillin and tropoelastin to form a complex. The complex has an elongated structure that supports end-to-end assembly. Cross-linking restricts the molecular motions of tropoelastin and fibrillin. Stabilisation may provide an initiating molecular mechanism for elastic fibre assembly.
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DOI：
10.1073/pnas.0601609103
发表时间：
2006-08-08
影响因子：
11.1
作者：
Baldock, Clair;Siegler, Veronique;Wess, Tim J.
通讯作者：
Wess, Tim J.
影响因子：
2.9
作者：
Clarke, AW;Wise, SG;Weiss, AS
通讯作者：
Weiss, AS
影响因子：
7.4
作者：
Katt WP;Antonyak MA;Cerione RA
通讯作者：
Cerione RA
影响因子：
4.4
作者：
ESSMANN, U;PERERA, L;PEDERSEN, LG
通讯作者：
PEDERSEN, LG
影响因子：
4.8
作者：
Bax, DV;Bernard, SE;Kielty, CM
通讯作者：
Kielty, CM