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) 的多分散性给分析其溶液特性（例如质量和粒径之间的关系）带来了挑战。与已知分子量的分子（例如蛋白质）相比，天然 HA 的宽质量范围（≤50 倍）使得分子表征变得困难且模糊。生物物理学研究表明，>MDa 的大 HA 表现得像随机线圈，而非常小的（例如 10 kDa）HA 表现得像棒。然而，在天然多分散 HA 中，这种构象转变的质量范围不容易确定。一些 HA 受体（例如 CD44 和 HARE）在结合 100-300 kDa 范围内的 HA 时启动信号响应，但较大的 MDa HA 则不会。使用非天然 HA 研究尺寸依赖性反应：纯化的窄尺寸范围 HA [Pandey MS、Baggenstoss BA、Washburn J、Harris EN、Weigel PH。 2013.内吞作用的透明质酸受体 (HARE) 响应 40-400 kDa（但不是更小或更高的透明质酸）激活 NF-κB 介导的基因表达。生物化学杂志。 288:14068–14079] 并且通过化学酶法制备的 Select-HA 尺寸范围非常窄 [Jing W, DeAngelis PL.288:14068–14079] 2004.单分散透明质酸聚合物的同步化学酶合成。生物化学杂志。 279：42345–42349]。在这里，我们使用尺寸排阻色谱和多角度光散射来确定约 60 种 29 至 1650 kDa 的非常窄尺寸制剂的重均摩尔质量和直径。 HA 质量与 HA 直径的比率显示在 150–250 kDa 尺寸范围（~65 nm）内发生转变。 HA 棒到线圈的转变发生在通过某些受体特异性激活细胞信号传导的尺寸范围内。 因此，大小特异性信号传导可能是由于独特的外部受体·HA构象变化，使得跨膜介导的细胞质结构域激活成为可能。或者，更有可能的是，过渡大小的 HA 可以使多个受体结合相同的 HA，从而创建新的内部信号有效的细胞质结构域复合物。