%0 Journal Article
%T Driving forces for condensation of synapsin are governed by sequence-encoded molecular grammars.
%A Hoffmann C
%A Ruff KM
%A Edu IA
%A Shinn MK
%A Tromm JV
%A King MR
%A Pant A
%A Ausserwöger H
%A Morgan JR
%A Knowles TPJ
%A Pappu RV
%A Milovanovic D
%J bioRxiv
%V 0
%N 0
%D 2024 Aug 4
%M 39131319
暂无%R 10.1101/2024.08.03.606464
%X 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.