Microbes have developed mechanisms to resist the host immune defenses and some elicit antitumor immune responses. About 6 million people are infected with Trypanosoma cruzi, the protozoan agent of Chagas' disease, the sixth neglected tropical disease worldwide. Eighty years ago, G. Roskin and N. Klyuyeva proposed that T. cruzi infection mediates an anti-cancer activity. This observation has been reproduced by several other laboratories, but no molecular basis has been proposed. We have shown that the highly pleiotropic chaperone calreticulin (TcCalr, formerly known as TcCRT), translocates from the parasite ER to the exterior, where it mediates infection. Similar to its human counterpart HuCALR (formerly known as HuCRT), TcCalr inhibits C1 in its capacity to initiate the classical pathway of complement activation. We have also proposed that TcCalr inhibits angiogenesis and it is a likely mediator of antitumor effects. We have generated several in silico structural TcCalr models to delimit a peptide (VC-TcCalr) at the TcCalr N-domain. Chemically synthesized VC-TcCalr did bind to C1q and was anti-angiogenic in Gallus gallus chorioallantoic membrane assays. These properties were associated with structural features, as determined in silico. VC-TcCalr, a strong dipole, interacts with charged proteins such as collagen-like tails and scavenger receptors. Comparatively, HuCALR has less polarity and spatial stability, probably due to at least substitutions of Gln for Gly, Arg for Lys, Arg for Asp and Ser for Arg that hinder protein-protein interactions. These differences can explain, at least in part, how TcCalr inhibits the complement activation pathway and has higher efficiency as an antiangiogenic and antitumor agent than HuCALR.

中文翻译：

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强调克鲁氏锥虫钙网蛋白的抗感染，抗血管生成和抗肿瘤特性的结构基础。

微生物已经开发出抵抗宿主免疫防御的机制，并引起一些抗肿瘤免疫反应。大约600万人感染了锥虫锥虫，锥虫是恰加斯氏病的原生动物，是全球第六种被忽视的热带病。八十年前，G。Roskin和N. Klyuyeva提出克氏锥虫感染具有抗癌活性。其他实验室也重现了这一观察结果，但尚未提出分子基础。我们已经显示，高度多效性的伴侣钙网蛋白（TcCalr，以前称为TcCRT），从寄生虫ER转运到外部，在此介导感染。TcCalr与人类对应的HuCALR（以前称为HuCRT）相似，它以启动补体激活经典途径的能力抑制C1。我们还提出了TcCalr抑制血管生成，它可能是抗肿瘤作用的介质。我们已经生成了几种计算机模拟的TcCalr结构模型，以在TcCalr N域上界定肽（VC-TcCalr）。化学合成的VC-TcCalr确实结合了C1q，并且在鸡胆囊尿囊膜测定中具有抗血管生成作用。这些特性与计算机确定的结构特征有关。VC-TcCalr是一种强偶极子，可与带电荷的蛋白质（如胶原样尾巴和清道夫受体）相互作用。相比之下，HuCALR具有较小的极性和空间稳定性，这可能是由于至少Gln取代了Gly，Arg取代了Lys，Arg取代了Asp和Ser取代了Arg阻碍了蛋白质-蛋白质相互作用。这些差异可以至少部分地解释