Effects of linker length on phase separation: lessons from the Rubisco-EPYC1 system of the algal pyrenoid
Effects of linker length on phase separation: lessons from the Rubisco-EPYC1 system of the algal pyrenoid
Abstract Biomolecular condensates are membraneless organelles formed via phase separation of macromolecules, typically consisting of bond-forming “stickers” connected by flexible “linkers”. Linkers have diverse roles, such as occupying space and facilitating interactions. To understand how linker length relative to other lengths affects condensation, we focus on the pyrenoid, which enhances photosynthesis in green algae. Specifically, we apply coarse-grained simulations and analytical theory to the pyrenoid proteins of Chlamydomonas reinhardtii: the rigid holoenzyme Rubisco and its flexible partner EPYC1. Remarkably, halving EPYC1 linker lengths decreases critical concentrations by ten-fold. We attribute this difference to the molecular “fit” between EPYC1 and Rubisco. Varying Rubisco sticker locations reveals that the native sites yield the poorest fit, thus optimizing phase separation. Surprisingly, shorter linkers mediate a transition to a gas of rods as Rubisco stickers approach the poles. These findings illustrate how intrinsically disordered proteins affect phase separation through the interplay of molecular length scales.
Zhang Yaojun、Wingreen Ned S.、Jonikas Martin C.、GrandPre Trevor、Pyo Andrew G. T.、Weiner Benjamin、Li Je-Luen
Center for the Physics of Biological Function, Princeton University||Department of Physics and Astronomy, Johns Hopkins University||Department of Biophysics, Johns Hopkins UniversityCenter for the Physics of Biological Function, Princeton University||Princeton Center for Theoretical Science, Princeton University||Department of Molecular Biology, Princeton University||Lewis-Sigler Institute for Integrative Genomics, Princeton UniversityHoward Hughes Medical Institute, Princeton University||Department of Molecular Biology, Princeton UniversityDepartment of Physics, Princeton University||Center for the Physics of Biological Function, Princeton University||Princeton Center for Theoretical Science, Princeton UniversityDepartment of Physics, Princeton University||Center for the Physics of Biological Function, Princeton UniversityDepartment of Physics, Princeton University||Center for the Physics of Biological Function, Princeton UniversityD. E. Shaw Research
生物物理学分子生物学生物科学现状、生物科学发展
Zhang Yaojun,Wingreen Ned S.,Jonikas Martin C.,GrandPre Trevor,Pyo Andrew G. T.,Weiner Benjamin,Li Je-Luen.Effects of linker length on phase separation: lessons from the Rubisco-EPYC1 system of the algal pyrenoid[EB/OL].(2025-03-28)[2025-05-18].https://www.biorxiv.org/content/10.1101/2023.06.11.544494.点此复制
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