RT Journal Article
SR Electronic
T1 Mechanistic insights of glucosome condensate formation by stochastic modeling approaches
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.06.27.497813
DO 10.1101/2022.06.27.497813
A1 Hye-Won Kang
A1 Luan Nguyen
A1 Songon An
A1 Minjoung Kyoung
YR 2022
UL http://biorxiv.org/content/early/2022/06/27/2022.06.27.497813.abstract
AB Human liver-type phosphofructokinase 1 (PFKL) has been shown to play a scaffolder role to recruit and organize glycolytic and gluconeogenic enzymes into a multienzyme metabolic condensate, the glucosome, that regulates glucose flux in living human cells. However, it has been challenging to characterize which factors control phase separation of PFKL and so glucosome condensates in a living cell, thus hampering to understand a mechanism of reversible glucosome formation and its functional contribution to human cells. In this work, we developed a stochastic model in silico using the principal of Langevin dynamics to investigate how biological properties of PFKL contribute to the formation of glucosome condensates. Molecular dynamics simulation using the Large-scale Atomic/Molecular Massively Parallel Simulator (LAMMPS) revealed the importance of an intermolecular interaction between PFKLs, an effective concentration of PFKL at a region of interest, and a pre-organization of its own self-assembly in formation of PFKL condensates and control of their sizes. Such biological properties that define intracellular dynamics of PFKL appear to be essential for phase separation of PFKL and thus formation of glucosome condensates. Collectively, our computational study provides mechanistic insights of glucosome formation, particularly an initiation step through the formation of PFKL condensates in living human cells.Competing Interest StatementThe authors have declared no competing interest.