The University of Liverpool, Institute of Systems, Molecular & Integrative Biology, Biosciences Building, Crown Street, Liverpool L69 7ZB, United Kingdom; Computational Biology Facility, MerseyBio, University of Liverpool, Crown Street, Liverpool L69 7ZB, United Kingdom.
The University of Liverpool, Institute of Systems, Molecular & Integrative Biology, Biosciences Building, Crown Street, Liverpool L69 7ZB, United Kingdom.
J Struct Biol. 2023 Sep;215(3):108010. doi: 10.1016/j.jsb.2023.108010. Epub 2023 Aug 6.
Repeat proteins are common in all domains of life and exhibit a wide range of functions. One class of repeat protein contains solenoid folds where the repeating unit consists of β-strands separated by tight turns. β-solenoids have distinguishing structural features such as handedness, twist, oligomerisation state, coil shape and size which give rise to their diversity. Characterised β-solenoid repeat proteins are known to form regions in bacterial and viral virulence factors, antifreeze proteins and functional amyloids. For many of these proteins, the experimental structure has not been solved, as they are difficult to crystallise or model. Here we use various deep learning-based structure-modelling methods to discover novel predicted β-solenoids, perform structural database searches to mine further structural neighbours and relate their predicted structure to possible functions. We find both eukaryotic and prokaryotic adhesins, confirming a known functional linkage between adhesin function and the β-solenoid fold. We further identify exceptionally long, flat β-solenoid folds as possible structures of mucin tandem repeat regions and unprecedentedly small β-solenoid structures. Additionally, we characterise a novel β-solenoid coil shape, the FapC Greek key β-solenoid as well as plausible complexes between it and other proteins involved in Pseudomonas functional amyloid fibres.
重复蛋白在所有生命领域中都很常见，具有广泛的功能。一类重复蛋白含有螺旋线折叠，其中重复单元由β-折叠组成，β-折叠之间由紧密的转弯隔开。β-螺旋线具有独特的结构特征，如手性、扭曲、寡聚状态、线圈形状和大小，这些特征导致了它们的多样性。已知特征性β-螺旋线重复蛋白存在于细菌和病毒毒力因子、抗冻蛋白和功能性淀粉样蛋白中。对于许多这些蛋白质，由于它们难以结晶或建模，因此尚未确定其实验结构。在这里，我们使用各种基于深度学习的结构建模方法来发现新的预测β-螺旋线，进行结构数据库搜索以挖掘更多的结构邻居，并将其预测结构与可能的功能联系起来。我们发现了真核生物和原核生物的黏附素，证实了黏附素功能与β-螺旋线折叠之间的已知功能联系。我们进一步确定了异常长而平的β-螺旋线折叠作为黏蛋白串联重复区域的可能结构，以及前所未有的小β-螺旋线结构。此外，我们还对一种新的β-螺旋线线圈形状，即 FapC 希腊钥匙β-螺旋线，以及它与参与假单胞菌功能性淀粉样纤维的其他蛋白质之间可能的复合物进行了表征。
