PDF(Pubmed)
Abstract：
Brain functioning relies on orchestrated synaptic vesicle dynamics and controlled neurotransmitter release. Multiple biomolecular condensates coexist at the pre- and post-synapse and they are driven by condensation that combines binding, phase separation, and percolation. In pre-synapses, intrinsically disordered regions (IDRs) of synaptic proteins are drivers of condensation that enable clustering of synaptic vesicles (SVs). Although sequences of IDRs are poorly conserved across evolution, our computational analysis reveals the existence of non-random compositional biases and sequence patterns (molecular grammars) in IDRs of pre-synaptic proteins. For example, synapsin-1, which is essential for condensation of SVs, contains a conserved valence of arginine residues and blocks of polar and proline residues that are segregated from one another along the linear sequence. We show that these conserved features are crucial for driving synapsin-1 condensation in vitro and in cells. Our results highlight how conserved molecular grammars drive the condensation of key proteins at the pre-synapse.
摘要：
大脑功能依赖于协调的突触小泡动力学和受控的神经递质释放。多个生物分子缩合物在突触前和突触后共存，它们由结合结合的缩合驱动，相分离,和渗滤。在突触前，突触蛋白的内在无序区域（IDR）是凝聚的驱动因素，能够使突触囊泡（SV）聚集。尽管IDR的序列在进化过程中保守性差，我们的计算分析揭示了突触前蛋白的IDR中存在非随机组成偏差和序列模式(分子语法).例如,突触素-1，它对SV的缩合至关重要，含有精氨酸残基的保守化合价和沿着线性序列彼此分离的极性和脯氨酸残基的区块。我们表明，这些保守的特征对于在体外和细胞中驱动突触素1缩合至关重要。我们的结果强调了保守的分子语法如何驱动突触前关键蛋白的凝聚。
