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bioRxiv · 10.1101/2019.12.18.881771

Phase separation-mediated formation of condensed GIT/PIX enzyme complex module for compartmentalized signaling

Zhu, J.·Zhou, Q.·Xia, Y.·Lin, L.·Li, J.·Peng, M.·Zhang, R.·Zhang, M.
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Abstract

Cells compartmentalize enzymes for broad physiological functions such as efficient metabolic reactions and spatiotemporally controlled signaling. A given enzyme or enzyme complex can participate in multiple cellular processes in response to different signal inputs by forming different cellular compartments. Here, we demonstrate that association of GIT1 and {beta}-Pix, a pair of GTPase regulatory enzymes involved in diverse cellular processes, leads to autonomous condensation of the complex via phase separation without additional scaffolding molecules. The atomic structure of the GIT/PIX complex reveals the molecular basis governing the phase separation-mediated condensation of the GIT1/{beta}-Pix complex. Importantly, the GIT1/{beta}-Pix condensates can function as a versatile modular membrane-less organelle- like structure for distinct cellular compartmentalization by binding to upstream proteins such as Paxillin in focal adhesions, Shank3 in neuronal synapses, and Scribble in cellular junctions. Thus, phase separation-mediated formation of condensed enzyme complexes provides a powerful way of dynamically concentrating limited amounts of cooperating enzymes to specific cellular compartments for optimal signaling.

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Zhu, J., Zhou, Q., Xia, Y., Lin, L., Li, J., Peng, M., Zhang, R., Zhang, M.. 2019-12-19. Phase separation-mediated formation of condensed GIT/PIX enzyme complex module for compartmentalized signaling. https://doi.org/10.1101/2019.12.18.881771

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