Kiss-Tóth Annamária, Dobson Laszlo, Péterfia Bálint, Ángyán Annamária F, Ligeti Balázs, Lukács Gergely, Gáspári Zoltán
Faculty of Information Technology and Bionics, Pázmány Péter Catholic University, Práter u. 50A, 1083 Budapest, Hungary.
3in-PPCU Research Group, 2500 Esztergom, Hungary.
Entropy (Basel). 2019 Aug 6;21(8):761. doi: 10.3390/e21080761.
The human postsynaptic density is an elaborate network comprising thousands of proteins, playing a vital role in the molecular events of learning and the formation of memory. Despite our growing knowledge of specific proteins and their interactions, atomic-level details of their full three-dimensional structure and their rearrangements are mostly elusive. Advancements in structural bioinformatics enabled us to depict the characteristic features of proteins involved in different processes aiding neurotransmission. We show that postsynaptic protein-protein interactions are mediated through the delicate balance of intrinsically disordered regions and folded domains, and this duality is also imprinted in the amino acid sequence. We introduce Diversity of Potential Interactions (DPI), a structure and regulation based descriptor to assess the diversity of interactions. Our approach reveals that the postsynaptic proteome has its own characteristic features and these properties reliably discriminate them from other proteins of the human proteome. Our results suggest that postsynaptic proteins are especially susceptible to forming diverse interactions with each other, which might be key in the reorganization of the postsynaptic density (PSD) in molecular processes related to learning and memory.
人类突触后致密区是一个由数千种蛋白质组成的复杂网络，在学习的分子事件和记忆形成中起着至关重要的作用。尽管我们对特定蛋白质及其相互作用的了解不断增加，但它们完整三维结构及其重排的原子级细节大多难以捉摸。结构生物信息学的进展使我们能够描绘参与不同神经传递过程的蛋白质的特征。我们表明，突触后蛋白质-蛋白质相互作用是通过内在无序区域和折叠结构域的微妙平衡介导的，这种二元性也印记在氨基酸序列中。我们引入了潜在相互作用多样性（DPI），这是一种基于结构和调控的描述符，用于评估相互作用的多样性。我们的方法表明，突触后蛋白质组具有其自身的特征，这些特性能够可靠地将它们与人类蛋白质组中的其他蛋白质区分开来。我们的结果表明，突触后蛋白质特别容易相互形成多样的相互作用，这可能是与学习和记忆相关的分子过程中突触后致密区（PSD）重组的关键。
