Disordered proteins: microphases or associative polymers? DOI Creative Commons
Martin Girard

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Окт. 11, 2024

We develop a surrogate model for low complexity disordered proteins, which allows us to generate sequences with quantifiable disorder. investigate properties of these sequences, and show that the sequence dependence radius gyration only arises in vicinity polymer collapse transition. Microphase propensity is shown be reliable predictor, outperforming state art methods, crossover region. predictions associative theory as limiting case, discuss its applicability.

Язык: Английский

Dipping contacts – a novel type of contact site at the interface between membraneless organelles and membranes DOI Creative Commons
Christian Hoffmann, Dragomir Milovanović

Journal of Cell Science, Год журнала: 2023, Номер 136(24)

Опубликована: Дек. 15, 2023

Liquid-liquid phase separation is a major mechanism for organizing macromolecules, particularly proteins with intrinsically disordered regions, in compartments not limited by membrane or scaffold. The cell can therefore be perceived as complex emulsion containing many of these membraneless organelles, also referred to biomolecular condensates, together numerous membrane-bound organelles. It currently unclear how such concoction operates allow intracellular trafficking, signaling and metabolic processes occur high spatiotemporal precision. Based on experimental observations synaptic vesicle condensates - organelle that fact packed membranes we present here the framework dipping contacts: novel type contact site between organelles membranes. In this Hypothesis, propose our contacts serve foundation investigate interface couples diffusion material properties biochemical occurring identity regulation especially critical case neurodegenerative diseases, where aberrant inclusions misfolded damaged underlie cellular pathology.

Язык: Английский

Процитировано

5

Rediscovering the intricacies of secretory granule biogenesis DOI Creative Commons
Felix Campelo, Meng Tian, Julia von Blume

и другие.

Current Opinion in Cell Biology, Год журнала: 2023, Номер 85, С. 102231 - 102231

Опубликована: Авг. 30, 2023

Язык: Английский

Процитировано

4

Transcription regulates the spatio-temporal dynamics of genes through micro-compartmentalization DOI Creative Commons

Hossein Salari,

Geneviève Fourel,

Daniel Jost

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Июль 19, 2023

Abstract Although our understanding of the involvement heterochromatin architectural factors in shaping nuclear organization is improving, there still ongoing debate regarding role active genes this process. In study, we utilize publicly-available Micro-C data from mouse embryonic stem cells to investigate relationship between gene transcription and 3D folding. Our analysis uncovers a nonmonotonic - globally positive correlation intragenic contact density Pol II occupancy, independent cohesin-based loop extrusion. Through development biophysical model integrating dynamics within polymer chromosome organization, demonstrate that II-mediated attractive interactions with limited valency transcribed regions yield quantitative predictions consistent chromosome-conformation-capture live-imaging experiments. work provides compelling evidence transcriptional activity shapes 4D genome through micro-compartmentalization.

Язык: Английский

Процитировано

2

Accurate Simulation of Coupling between Protein Secondary Structure and Liquid-Liquid Phase Separation DOI Creative Commons
Yumeng Zhang, Shanlong Li, Xiping Gong

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Авг. 23, 2023

Abstract Intrinsically disordered proteins (IDPs) frequently mediate liquid-liquid phase separation (LLPS) that underlies the formation of membraneless organelles. Together with theory and experiment, efficient coarse-grained (CG) simulations have been instrumental in understanding sequence- specific IDPs. However, widely-used Cα-only models are severely limited capturing peptide nature IDPs, including backbone-mediated interactions effects secondary structures, LLPS. Here, we describe a hybrid resolution (HyRes) protein model for accurate description backbone transient structures With an atomistic side chains, HyRes accurately predicts residue helical propensity chain dimension monomeric Using GY-23 as system, show is enough direct simulation spontaneous separation, at same time to resolve single mutations. also successfully predict increased beta-sheet condensate, consistent available experimental data. We further utilize study TPD-43, where several disease-related mutants conserved region (CR) shown affect residual helicities modulate LLPS propensity. The recapitulate effect these on helicity TDP-43 CR. Analyses reveal balance between sidechain-mediated interactions, but not itself, actually determines believe represents important advance molecular will help elucidate coupling IDP separation.

Язык: Английский

Процитировано

1

Disordered proteins: microphases or associative polymers? DOI Creative Commons
Martin Girard

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Окт. 11, 2024

We develop a surrogate model for low complexity disordered proteins, which allows us to generate sequences with quantifiable disorder. investigate properties of these sequences, and show that the sequence dependence radius gyration only arises in vicinity polymer collapse transition. Microphase propensity is shown be reliable predictor, outperforming state art methods, crossover region. predictions associative theory as limiting case, discuss its applicability.

Язык: Английский

Процитировано

0