Interactions between the breast cancer-associated MUC1 mucins and C-type lectin characterized by optical tweezers.
Interactions between the breast cancer-associated MUC1 mucins and C-type lectin characterized by optical tweezers.
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DOI：
10.1371/journal.pone.0175323
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Sletmoen M
中科院分区：
文献类型：
--
作者：
Hadjialirezaei S;Picco G;Beatson R;Burchell J;Stokke BT;Sletmoen M
碳水化合物-蛋白质相互作用控制着生物系统中的许多关键过程，包括细胞识别事件。我们使用灵敏的力探针光镊来量化MGL凝集素和携带癌症相关聚糖抗原粘蛋白Tn和STn的MUC 1之间发生的相互作用。在约40 pN/s的力加载速率下，确定MUC 1（Tn）-MGL和MUC 1（STn）-MGL相互作用的解结合力为7.6±1.1 pN和7.1±1.1 pN。相互作用强度随着力加载速率的增加而增加，在力加载速率为约310 pN/s时，分别为27.1±4.4和36.9±3.6 pN。MGL和MUC 1（ST）之间没有检测到相互作用，MUC 1的糖型也由乳腺癌细胞表达。有趣的是，这种聚糖（ST）可以在正常细胞表达的蛋白质上发现，尽管在这种情况下不在MUC 1上。此外，GalNAc修饰的聚乙二醇在被迫与MGL解结合时显示出与MUC 1（Tn）和MUC 1（STn）相似的断裂力，表明GalNAc是这些相互作用中的必需基团。由于STn聚糖装饰比Tn聚糖更频繁地发现于癌的表面上，因此携带STn的MUC 1与MGL的结合可能更具生理相关性，并且可能部分地负责表达STn的肿瘤的一些特征。
Carbohydrate–protein interactions govern many crucial processes in biological systems including cell recognition events. We have used the sensitive force probe optical tweezers to quantify the interactions occurring between MGL lectins and MUC1 carrying the cancer-associated glycan antigens mucins Tn and STn. Unbinding forces of 7.6±1.1 pN and 7.1±1.1 pN were determined for the MUC1(Tn)—MGL and MUC1(STn)—MGL interactions, at a force loading rate of ~40 pN/s. The interaction strength increased with increasing force loading rate, to 27.1±4.4 and 36.9±3.6 pN at a force loading rate of ~ 310 pN/s. No interactions were detected between MGL and MUC1(ST), a glycoform of MUC1 also expressed by breast carcinoma cells. Interestingly, this glycan (ST) can be found on proteins expressed by normal cells, although in this case not on MUC1. Additionally, GalNAc decorated polyethylene glycol displayed similar rupture forces as observed for MUC1(Tn) and MUC1(STn) when forced to unbind from MGL, indicating that GalNAc is an essential group in these interactions. Since the STn glycan decoration is more frequently found on the surface of carcinomas than the Tn glycan, the binding of MUC1 carrying STn to MGL may be more physiologically relevant and may be in part responsible for some of the characteristics of STn expressing tumours.