Unique Conformation in a Natural Interruption Sequence of Type XIX Collagen Revealed by Its High-Resolution Crystal Structure
Unique Conformation in a Natural Interruption Sequence of Type XIX Collagen Revealed by Its High-Resolution Crystal Structure
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高分辨率晶体结构揭示了 XIX 型胶原蛋白自然中断序列中的独特构象
DOI：
10.1021/acs.biochem.7b01010
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发表时间：
2018
期刊：
影响因子：
2.9
通讯作者：
Liu Jinsong
中科院分区：
文献类型：
--
作者：
Xu Tingting;Zhou Cong Zhao;Xiao Jianxi;Liu Jinsong
非纤维胶原蛋白中自然发生的中断在分子柔性、胶原蛋白降解和配体结合中起关键作用。中断序列的结构特征及其功能的分子基础尚未得到很好的研究。在这里，我们专注于G5 G型自然中断序列G-POALO-G从人类XIX型胶原蛋白，同源三聚体胶原蛋白，因为这个序列具有不同的属性相比，在胶原蛋白模拟肽的病理相似的Gly突变序列。我们测定了主客体肽（Ⅲ）3-GPOALO-（Ⅳ）4的晶体结构，两种晶型的分辨率为1.03 nm。在这些结构中，中断区对三螺旋带来局部中断，并对整个分子引入具有相同方向偏好的轻微6-8°弯曲，这可能在结构上对应于XIX型胶原中的第一生理扭结位点。此外，在G5 G中断位点，Ala和Leu残基的存在，都与游离的N-H基团，允许形成更直接和水介导的链间氢键比在相关的Gly → Ala结构。这可以部分解释不同中断之间的热稳定性差异。此外，我们的结构提供了一个详细的视图，这样的中断区的动态特性相对于氢键拓扑结构，扭转角，和螺旋参数。我们的研究结果，第一次，也确定了锌的三重螺旋的末端结合。这些发现将揭示中断序列如何影响胶原分子的构象，并为进一步的功能研究提供结构基础。
Naturally occurring interruptions in nonfibrillar collagen play key roles in molecular flexibility, collagen degradation, and ligand binding. The structural feature of the interruption sequences and the molecular basis for their functions have not been well studied. Here, we focused on a G5G type natural interruption sequence G-POALO-G from human type XIX collagen, a homotrimer collagen, as this sequence possesses distinct properties compared with those of a pathological similar Gly mutation sequence in collagen mimic peptides. We determined the crystal structures of the host–guest peptide (GPO)3-GPOALO-(GPO)4to 1.03 Å resolution in two crystal forms. In these structures, the interruption zone brings localized disruptions to the triple helix and introduces a light 6–8° bend with the same directional preference to the whole molecule, which may correspond structurally to the first physiological kink site in type XIX collagen. Furthermore, at the G5G interruption site, the presence of Ala and Leu residues, both with free N–H groups, allows the formation of more direct and water-mediated interchain hydrogen bonds than in the related Gly → Ala structure. These could partly explain the difference in thermal stability between the different interruptions. In addition, our structures provide a detailed view of the dynamic property of such an interrupted zone with respect to hydrogen bonding topology, torsion angles, and helical parameters. Our results, for the first time, also identified the binding of zinc to the end of the triple helix. These findings will shed light on how the interruption sequence influences the conformation of the collagen molecule and provide a structural basis for further functional studies.