The polydispersity of hyaluronan (HA) presents challenges for analyzing its solution properties, such as the relationship between mass and particle size. The broad mass range of natural HA (≤50-fold) makes molecular characterization difficult and ambiguous compared to molecules with known molecular weights (e.g., proteins). Biophysical studies show that large >MDa HA behaves like a random coil, whereas very small (e.g., 10 kDa) HA behaves like a rod. However, the mass range for this conformational transition is not easily determined in natural polydisperse HA. Some HA receptors (e.g., CD44 and HARE) initiate signaling responses upon binding HA in the 100–300 kDa range, but not larger MDa HA. Size-dependent responses are studied using nonnatural HA: purified narrow-size range HA [Pandey MS, Baggenstoss BA, Washburn J, Harris EN, Weigel PH. 2013. The hyaluronan receptor for endocytosis (HARE) activates NF-κB-mediated gene expression in response to 40–400 kDa, but not smaller or sarger, hyaluronans. J Biol Chem. 288:14068–14079] and very narrow size range Select-HA made chemo-enzymatically [Jing W, DeAngelis PL. 2004. Synchronized chemoenzymatic synthesis of monodisperse hyaluronan polymers. J Biol Chem. 279:42345–42349]. Here, we used size exclusion chromatography and multiangle light scattering to determine the weight-average molar mass and diameter of ~60 very narrow size preparations from 29 to 1650 kDa. The ratio of HA mass to HA diameter showed a transition in the 150–250 kDa size range (~65 nm). The HA rod-to-coil transition occurs within the size range that specifically activates cell signaling by some receptors. Thus, size-specific signaling could be due to unique external receptor•HA conformation changes that enable transmembrane-mediated activation of cytoplasmic domains. Alternatively and more likely, transition-size HA may enable multiple receptors to bind the same HA, creating new internal signal-competent cytoplasmic domain complexes.

中文翻译：

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激活透明质酸受体信号传导的200 kDa透明质酸有何特别之处？

透明质酸（HA）的多分散性为分析其溶液性质（例如质量与粒径之间的关系）提出了挑战。与具有已知分子量的分子（例如蛋白质）相比，天然HA的广泛质量范围（≤50倍）使分子表征变得困难且模棱两可。生物物理研究表明，> MDa大的HA的行为类似于无规卷曲，而很小的HA（例如10 kDa）的行为类似于棒状。但是，在天然多分散HA中不容易确定该构象转变的质量范围。一些HA受体（例如CD44和HARE）在结合HA的100–300 kDa范围内会启动信号传导反应，但对较大的MDa HA无效。使用非天然HA：纯化的窄尺寸HA [Pandey MS，Baggenstoss BA，Washburn J，Harris EN，Weigel PH。2013。内吞的透明质酸受体（HARE）激活NF-κB介导的基因表达，以响应40-400 kDa，但较小或更不透明的透明质酸。J生物化学。288：14068–14079]和选择范围非常狭窄的Select-HA化学酶法制备[Jing W，DeAngelis PL。2004。同步化学合成单分散透明质酸聚合物。J生物化学。279：42345–42349]。在这里，我们使用尺寸排阻色谱法和多角度光散射法测定了29至1650 kDa的约60种非常窄尺寸制剂的重均摩尔质量和直径。HA质量与HA直径之比在150–250 kDa尺寸范围（〜65 nm）中显示出过渡。HA杆到线圈的过渡发生在通过某些受体特异性激活细胞信号转导的大小范围内。因此，大小特异性信号可能是由于独特的外部受体•HA构象变化，使跨膜介导的胞质域激活。替代地并且更可能地，过渡大小的HA可能使多个受体结合相同的HA，从而产生新的具有内部信号功能的细胞质结构域复合物。