The molecular basis for cellular function of intrinsically disordered protein regions

AS Holehouse, BB Kragelund - Nature Reviews Molecular Cell Biology, 2024 - nature.com
Intrinsically disordered protein regions exist in a collection of dynamic interconverting
conformations that lack a stable 3D structure. These regions are structurally heterogeneous …

Liquid–liquid phase separation in crowded environments

AAM André, E Spruijt - International Journal of Molecular Sciences, 2020 - mdpi.com
Biomolecular condensates play a key role in organizing cellular fluids such as the cytoplasm
and nucleoplasm. Most of these non-membranous organelles show liquid-like properties …

Macromolecular crowding is more than hard-core repulsions

SL Speer, CJ Stewart, L Sapir… - Annual Review of …, 2022 - annualreviews.org
Cells are crowded, but proteins are almost always studied in dilute aqueous buffer. We
review the experimental evidence that crowding affects the equilibrium thermodynamics of …

Intrinsically disordered regions are poised to act as sensors of cellular chemistry

D Moses, GM Ginell, AS Holehouse… - Trends in biochemical …, 2023 - cell.com
Intrinsically disordered proteins and protein regions (IDRs) are abundant in eukaryotic
proteomes and play a wide variety of essential roles. Instead of folding into a stable …

The centrosome is a selective condensate that nucleates microtubules by concentrating tubulin

JB Woodruff, BF Gomes, PO Widlund, J Mahamid… - Cell, 2017 - cell.com
Centrosomes are non-membrane-bound compartments that nucleate microtubule arrays.
They consist of nanometer-scale centrioles surrounded by a micron-scale, dynamic …

Self-interaction of NPM1 modulates multiple mechanisms of liquid–liquid phase separation

DM Mitrea, JA Cika, CB Stanley, A Nourse… - Nature …, 2018 - nature.com
Nucleophosmin (NPM1) is an abundant, oligomeric protein in the granular component of the
nucleolus with roles in ribosome biogenesis. Pentameric NPM1 undergoes liquid–liquid …

The contribution of intrinsically disordered regions to protein function, cellular complexity, and human disease

MM Babu - Biochemical Society Transactions, 2016 - portlandpress.com
In the 1960s, Christian Anfinsen postulated that the unique three-dimensional structure of a
protein is determined by its amino acid sequence. This work laid the foundation for the …

Conformational expansion of tau in condensates promotes irreversible aggregation

J Wen, L Hong, G Krainer, QQ Yao… - Journal of the …, 2021 - ACS Publications
Liquid–liquid phase separation (LLPS) of proteins into biomolecular condensates has
emerged as a fundamental principle underpinning cellular function and malfunction. Indeed …

What macromolecular crowding can do to a protein

IM Kuznetsova, KK Turoverov, VN Uversky - International journal of …, 2014 - mdpi.com
The intracellular environment represents an extremely crowded milieu, with a limited amount
of free water and an almost complete lack of unoccupied space. Obviously, slightly salted …

When phased without water: biophysics of cellular desiccation, from biomolecules to condensates

PS Romero-Perez, Y Dorone, E Flores… - Chemical …, 2023 - ACS Publications
The molecular machinery that enables life has evolved in water, yet many of the organisms
around us are able to survive even extreme desiccation. Especially remarkable are single …