Single-Molecule Unbinding Forces between the Polysaccharide Hyaluronan and Its Binding Proteins.
Single-Molecule Unbinding Forces between the Polysaccharide Hyaluronan and Its Binding Proteins.
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DOI：
10.1016/j.bpj.2018.05.014
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发表时间：
2018-06-19
影响因子：
3.4
通讯作者：
Richter RP
中科院分区：
文献类型：
--
作者：
Bano F;Tammi MI;Kang DW;Harris EN;Richter RP
细胞外多糖透明质酸(HA)广泛存在于所有脊椎动物组织中，其各种功能编码在与HA结合蛋白(透明质粘附素)形成的超分子复合体和基质中。在组织中，这些超分子结构经常受到机械应力的影响，但这如何影响分子间的成键在很大程度上是未知的。在这里，我们使用最近开发的单分子力谱平台来分析和比较HA与来自Link模块超家族的一组透明粘附素之间的机械强度，即蛋白多糖与软骨连接蛋白、蛋白多糖Versican、炎症相关蛋白TSG-6、HA内吞作用受体(稳定蛋白-2/HARE)和HA受体CD44。我们发现，这些透明粘附素的抗拉应力与HA结合域的大小有关。观察到A型亚组成员的平均破裂力最低(即具有最短的HA结合结构域；TSG-6和HARE)。相反，聚集素与软骨连接蛋白(C型亚基中的两个成员，即HA结合域最长的两个成员)和HA形成的键的机械稳定性与高亲和力的链霉亲和素⋅生物素键相当，甚至更好。讨论了HA⋅透明粘附素受力解离的分子机制，为HA⋅透明粘附素复合体和富含HA的细胞外基质的力学性能奠定了基础。
The extracellular polysaccharide hyaluronan (HA) is ubiquitous in all vertebrate tissues, where its various functions are encoded in the supramolecular complexes and matrices that it forms with HA-binding proteins (hyaladherins). In tissues, these supramolecular architectures are frequently subjected to mechanical stress, yet how this affects the intermolecular bonding is largely unknown. Here, we used a recently developed single-molecule force spectroscopy platform to analyze and compare the mechanical strength of bonds between HA and a panel of hyaladherins from the Link module superfamily, namely the complex of the proteoglycan aggrecan and cartilage link protein, the proteoglycan versican, the inflammation-associated protein TSG-6, the HA receptor for endocytosis (stabilin-2/HARE), and the HA receptor CD44. We find that the resistance to tensile stress for these hyaladherins correlates with the size of the HA-binding domain. The lowest mean rupture forces are observed for members of the type A subgroup (i.e., with the shortest HA-binding domains; TSG-6 and HARE). In contrast, the mechanical stability of the bond formed by aggrecan in complex with cartilage link protein (two members of the type C subgroup, i.e., with the longest HA-binding domains) and HA is equal or even superior to the high affinity streptavidin⋅biotin bond. Implications for the molecular mechanism of unbinding of HA⋅hyaladherin bonds under force are discussed, which underpin the mechanical properties of HA⋅hyaladherin complexes and HA-rich extracellular matrices.
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DOI：
10.1073/pnas.0806085105
发表时间：
2008-10-14
影响因子：
11.1
作者：
Dudko, Olga K.;Hummer, Gerhard;Szabo, Attila
通讯作者：
Szabo, Attila
影响因子：
2.3
作者：
Falkowski, M;Schledzewski, K;Goerdt, S
通讯作者：
Goerdt, S
影响因子：
16.8
作者：
Banerji, Suneale;Wright, Alan J.;Jackson, David G.
通讯作者：
Jackson, David G.
影响因子：
3.4
作者：
Evans, E;Ritchie, K
通讯作者：
Ritchie, K
影响因子：
3.4
作者：
Christophis, Christof;Taubert, Isabel;Rosenhahn, Axel
通讯作者：
Rosenhahn, Axel