@article{200931,
  author = {GrandPre T and Zhang Y and Pyo AGT and Weiner B and Li J and Jonikas MC and Wingreen NS},
  title = {Impact of Linker Length on Biomolecular Condensate Formation},
  abstract = {<p>Biomolecular condensates are membraneless organelles formed via phase separation of macromolecules, typically consisting of bond-forming {\textquotedblleft}stickers{\textquotedblright} connected by flexible {\textquotedblleft}linkers.{\textquotedblright} 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 <em>Chlamydomonas reinhardtii</em>: the rigid holoenzyme Rubisco and its flexible partner EPYC1. Remarkably, halving EPYC1 linker lengths decreases critical concentrations by tenfold. We attribute this difference to the molecular {\textquotedblleft}fit,{\textquotedblright} i.e., the number of stickers of EPYC1 that can bind to a single Rubisco given the constraint of EPYC1 linker length. We find an inverse relationship between molecular fit and the tendency of EPYC1 and Rubisco to phase separate. Moreover, by computationally varying Rubisco sticker locations we discover that the naturally occurring sticker locations yield the poorest fit for all EPYC1 linker lengths; thus the natural locations optimize 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.</p>},
  year = {2023},
  journal = {PRX Life 2023:1, 023013.},
}