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首页> 外文期刊>IUCrJ >Structures of parasite calreticulins provide insights into their flexibility and dual carbohydrate/peptide-binding properties
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Structures of parasite calreticulins provide insights into their flexibility and dual carbohydrate/peptide-binding properties

机译：寄生虫钙网蛋白的结构提供了对其柔韧性和碳水化合物/肽双重结合特性的深刻见解

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Calreticulin (CRT) is a multifaceted protein, initially discovered as an endoplasmic reticulum (ER) chaperone protein, that is essential in calcium metabolism. Various implications in cancer, early development and immunology have been discovered more recently for CRT, as well as its role as a dominant `eat-me' prophagocytic signal. Intriguingly, cell-surface exposure/secretion of CRT is among the infective strategies used by parasites such as Trypanosoma cruzi, Entamoeba histolytica, Taenia solium, Leishmania donovani and Schistosoma mansoni. Because of the inherent flexibility of CRTs, their analysis by X-ray crystallography requires the design of recombinant constructs suitable for crystallization, and thus only the structures of two very similar mammalian CRT lectin domains are known. With the X-ray structures of two distant parasite CRTs, insights into species structural determinants that might be harnessed to fight against the parasites without affecting the functions of the host CRT are now provided. Moreover, although the hypothesis that CRT can exhibit both open and closed conformations has been proposed in relation to its chaperone function, only the open conformation has so far been observed in crystal structures. The first evidence is now provided of a complex conformational transition with the junction reoriented towards P-domain closure. SAXS experiments also provided additional information about the flexibility of T. cruzi CRT in solution, thus complementing crystallographic data on the open conformation. Finally, regarding the conserved lectin-domain structure and chaperone function, evidence is provided of its dual carbohydrate/protein specificity and a new scheme is proposed to interpret such unusual substrate-binding properties. These fascinating features are fully consistent with previous experimental observations, as discussed considering the broad spectrum of CRT sequence conservations and differences.
机译：钙网蛋白（CRT）是一种多方面的蛋白质，最初被发现为内质网（ER）伴侣蛋白，在钙代谢中必不可少。最近，对于CRT，其在癌症，早期发展和免疫学方面的各种意义及其作为主要的“吞噬”前吞噬信号的作用也被发现。有趣的是，CRT的细胞表面暴露/分泌是克鲁氏锥虫，溶血性变形杆菌，En虫，利什曼原虫和诺曼氏血吸虫等寄生虫所使用的感染策略之一。由于CRT固有的柔韧性，通过X射线晶体学对其进行分析需要设计适合结晶的重组构建体，因此仅已知两个非常相似的哺乳动物CRT凝集素结构域的结构。现在，利用两个遥远的寄生虫CRT的X射线结构，可以深入了解物种结构决定因素，这些决定因素可以用来对抗寄生虫而不影响宿主CRT的功能。而且，尽管已经提出了关于CRT可以同时表现出其开放性和封闭性构象的假说，但迄今为止，在晶体结构中仅观察到开放性构象。现在提供了一个复杂的构象转变的初步证据，其中连接朝向P结构域闭合。 SAXS实验还提供了有关T. cruzi CRT在溶液中的灵活性的其他信息，从而补充了开放构象上的晶体学数据。最后，关于保守的凝集素结构域结构和伴侣功能，提供了其双重碳水化合物/蛋白质特异性的证据，并提出了一种新的方案来解释这种异常的底物结合特性。这些引人入胜的特征与以前的实验观察完全一致，如前所述，考虑到广泛的CRT序列保守性和差异性。

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