Backbone dynamics of homologous fibronectin type III cell adhesion domains from fibronectin and tenascin
Backbone dynamics of homologous fibronectin type III cell adhesion domains from fibronectin and tenascin
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DOI：
10.1016/s0969-2126(97)00248-7
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发表时间：
1997-07-15
期刊：
影响因子：
5.7
通讯作者：
Palmer, AG
中科院分区：
文献类型：
--
作者：
Carr, PA;Erickson, HP;Palmer, AG
背景资料：纤连蛋白III型结构域被发现是多种多结构域蛋白质（包括细胞外基质蛋白）中的折叠结构域。这些结构域的子集采用Arg-Gly-Asp（RGD）三肽基序来介导与细胞表面受体（整联蛋白）的接触。该基序介导多种生物过程中的蛋白质-蛋白质相互作用，例如组织发育、伤口愈合和转移。通过III型结构域的细胞粘附的亲和力和特异性的分子基础尚未明确建立。来自纤连蛋白的第十个III型结构域（FNfn 10）和来自生腱蛋白-C的第三个III型结构域（TNfn 3）具有27%的序列同一性，并且共享相同的总体蛋白质折叠，但是在不同的结构背景中呈现RGD基序。RGD基序的动力学性质可能影响FNfn 10和TNfn 3结构域的特异性和亲和力。这些结构同源的蛋白质的结构动力学相关性可能会揭示共同的分子特征，这是重要的蛋白质的动力学properties.Results：的分子内动力学的蛋白质骨架的FNfn 10和TNfn 3的N-15核自旋弛豫进行了研究。FNfn 10中含有RGD基序的FG环在皮秒至纳秒时间尺度上表现出广泛的灵活性，但未观察到微秒至毫秒时间尺度上的运动。TNfn 3中的等效区域与二级结构的规则元素一样刚性。在FNfn 10中，CC'环路在皮秒-纳秒时间尺度上也比TNfn 3中更灵活。在FNfn 10和TNfn 3的β链A和B中观察到构象交换，反映了微秒-毫秒时间尺度上的灵活性。结论：FNfn 10和TNfn 3的结构比较揭示了与其不同动力学性质相关的一些特征。FNfn 10中环的较大幅度运动与这些区域的灵活性促进多个受体对纤连蛋白的诱导拟合识别的假设一致：类似地，TNfn 3的更刚性的环可能反映了对特定整合素的更大特异性。同源II型结构域的结构特征和动力学性质之间的相关性表明氢键和疏水堆积对蛋白质动力学波动的影响。
Background: Fibronectin type III domains are found as autonomously-folded domains in a large variety of multidomain proteins, including extracellular matrix proteins. A subset of these domains employ an Arg-Gly-Asp (RGD) tripeptide motif to mediate contact with cell-surface receptors (integrins). This motif mediates protein-protein interactions in a diverse range of biological processes, such as in tissue development, wound healing and metastasis. The molecular basis for affinity and specificity of cell adhesion via type III domains has not been clearly established. The tenth type III domain from fibronectin (FNfn10) and the third type III domain from tenascin-C (TNfn3) have 27% sequence identity and share the same overall protein fold, but present the RGD motifs in different structural contexts. The dynamical properties of the RGD motifs may affect the specificity and affinity of the FNfn10 and TNfn3 domains. Structure-dynamics correlations for these structurally homologous proteins may reveal common molecular features which are important to the dynamical properties of proteins.Results: The intramolecular dynamics of the protein backbones of FNfn10 and TNfn3 have been studied by N-15 nuclear spin relaxation. The FG loop in FNfn10, which contains the RGD motif, exhibits extensive flexibility on picosecond to nanosecond timescales, but motions on microsecond to millisecond timescales are not observed. The equivalent region in TNfn3 is as rigid as regular elements of secondary structure. The CC' loop also is more flexible on picosecond-nanosecond timescales in FNfn10 than in TNfn3. Conformational exchange, reflecting flexibility on microsecond-millisecond timescales, is observed in beta strands A and B of both FNfn10 and TNfn3.Conclusions: Comparison of the structures of the FNfn10 and TNfn3 reveals several features related to their different dynamical properties. The larger amplitude motions of loops in FNfn10 are consistent with the hypothesis that flexibility of these regions facilitates induced-fit recognition of fibronectin by multiple receptors: Similarly, the more rigid loops of TNfn3 may reflect greater specificity for particular integrins. The correlations observed between structural features and dynamical properties of the homologous type II[ domains indicate the influence of hydrogen bonding and hydrophobic packing on dynamical fluctuations in proteins.