K M Ahsanul Kabir, Takuya Takahashi, Takeshi Kikuchi
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引用次数: 0
Abstract
Background: Protein folding is a complex process in which amino acid sequences encode the information required for a polypeptide chain to fold into its functional three-dimensional (3D) structure. Many proteins share common substructures and recurring secondary structure elements that contribute to similar 3D folding patterns, even across different protein families. This study examines two distinct groups of proteins, the RNase A-like fold and the trypsin-like serine protease fold, classified by SCOPe. These proteins share only some substructures that contribute to their folding cores. Despite minimal sequence identity, they exhibit partial structural similarities in their 3D topologies. We used a sequence-based approach, including inter-residue average distance statistics and contact frequency prediction, to explore these folding characteristics. Structural observations guided further analyses of conserved hydrophobic residue packing, highlighting key folding units within each fold.
Results: Our analysis predicted two compact regions within each protein group. Interactions between these regions form a partially shared topology. We identified conserved hydrophobic residues critical to these interactions, suggesting a common mechanism for establishing these structural features. Despite overall structural differences between the RNase A-like and trypsin-like folds, our findings emphasize the presence of a shared partial folding core.
Conclusions: The partially shared structural features in the RNase A-like and trypsin-like serine protease folds reflect a convergent folding mechanism. This mechanism underscores the evolutionary adaptation of protein folding, where distinct folds can still retain critical, conserved structural motifs. These findings highlight how proteins with overall different topologies can evolve to share key folding features, demonstrating the elegance and efficiency of protein evolution.
背景:蛋白质折叠是一个复杂的过程,其中氨基酸序列编码多肽链折叠成其功能三维(3D)结构所需的信息。许多蛋白质具有共同的亚结构和重复的二级结构元素,这些元素有助于形成相似的3D折叠模式,甚至在不同的蛋白质家族中也是如此。本研究检查了两组不同的蛋白质,RNase a样折叠和胰蛋白酶样丝氨酸蛋白酶折叠,按SCOPe分类。这些蛋白质只有一些共同的亚结构有助于它们的折叠核心。尽管具有最小的序列同一性,但它们在三维拓扑结构中表现出部分结构相似性。我们使用基于序列的方法,包括残基间平均距离统计和接触频率预测,来探索这些折叠特征。结构观察指导了进一步的保守疏水残基堆积分析,突出了每个褶皱内的关键折叠单元。结果:我们的分析预测了每个蛋白质组内的两个紧凑区域。这些区域之间的交互形成了部分共享的拓扑结构。我们确定了对这些相互作用至关重要的保守疏水残基,提出了建立这些结构特征的共同机制。尽管RNase a -like和胰蛋白酶-like折叠在整体结构上存在差异,但我们的研究结果强调了共享部分折叠核心的存在。结论:RNase a样丝氨酸蛋白酶和胰蛋白酶样丝氨酸蛋白酶褶皱部分共享的结构特征反映了一种趋同的折叠机制。这种机制强调了蛋白质折叠的进化适应性,其中不同的折叠仍然可以保留关键的,保守的结构基序。这些发现强调了具有整体不同拓扑结构的蛋白质如何进化以共享关键折叠特征,展示了蛋白质进化的优雅和效率。