Institute of Biomedical and Pharmaceutical Sciences, Hubei University of Technology, Wuhan, 430068, China.
Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei University of Technology, Wuhan, China.
Protein J. 2018 Feb;37(1):13-20. doi: 10.1007/s10930-017-9747-5.
Three-dimensional (3D) domain swapping is a mechanism to form protein oligomers. It has been proposed that several factors, including proline residues in the hinge region, may affect the occurrence of 3D domain swapping. Although introducing prolines into the hinge region has been found to promote domain swapping for some proteins, the opposite effect has also been observed in several studies. So far, how proline affects 3D domain swapping remains elusive. In this work, based on a large set of 3D domain-swapped structures, we performed a systematic analysis to explore the correlation between the presence of proline in the hinge region and the occurrence of 3D domain swapping. We further analyzed the conformations of proline and pre-proline residues to investigate the roles of proline in 3D domain swapping. We found that more than 40% of the domain-swapped structures contained proline residues in the hinge region. Unexpectedly, conformational transitions of proline residues were rarely observed upon domain swapping. Our analyses showed that hinge regions containing proline residues preferred more extended conformations, which may be beneficial for the occurrence of domain swapping by facilitating opening of the exchanged segments.
三维（3D）结构域交换是形成蛋白质寡聚体的一种机制。有人提出，包括铰链区域脯氨酸残基在内的几个因素可能会影响 3D 结构域交换的发生。尽管在铰链区域引入脯氨酸已被发现可促进某些蛋白质的结构域交换，但在几项研究中也观察到了相反的效果。迄今为止，脯氨酸如何影响 3D 结构域交换仍然难以捉摸。在这项工作中，我们基于一大组 3D 结构域交换结构，进行了系统分析，以探讨铰链区域脯氨酸的存在与 3D 结构域交换发生之间的相关性。我们进一步分析了脯氨酸和前脯氨酸残基的构象，以研究脯氨酸在 3D 结构域交换中的作用。我们发现，超过 40%的结构域交换结构在铰链区域含有脯氨酸残基。出乎意料的是，在结构域交换过程中很少观察到脯氨酸残基的构象转变。我们的分析表明，含有脯氨酸残基的铰链区域倾向于更伸展的构象，这可能有利于通过促进交换片段的打开来促进结构域交换的发生。
