Biomolecular condensates can function as inherent catalysts

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

Опубликована: Июль 10, 2024

We report the discovery that chemical reactions such as ATP hydrolysis can be catalyzed by condensates formed intrinsically disordered proteins (IDPs), which themselves lack any intrinsic ability to function enzymes. This inherent catalytic feature of derives from electrochemical environments and electric fields at interfaces are direct consequences phase separation. The we studied were capable catalyzing diverse reactions, including radical-dependent breakdown whereby fully decomposes adenine multiple carbohydrates. distinguishes naturally occurring ATPases, only catalyze dephosphorylation ATP. Interphase interfacial properties tuned via sequence design, thus enabling control over catalysis through sequence-dependent features condensates. Incorporation hydrolase-like synthetic into live cells enables activation transcriptional circuits depend on products reactions. Inherent functions condensates, emergent separation, likely affect metabolic regulation in cells.

Язык: Английский

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Hydrogen-Bonded Network of Water in Phase-Separated Biomolecular Condensates

The Journal of Physical Chemistry Letters, Год журнала: 2024, Номер 15(30), С. 7724 - 7734

Опубликована: Июль 23, 2024

Biomolecular condensates formed via phase separation of intrinsically disordered proteins/regions (IDPs/IDRs) and nucleic acids are associated with cell physiology disease. Water makes up for ∼60-70% the condensate volume is thought to influence complex interplay chain-chain chain-solvent interactions, modulating mesoscale properties condensates. The behavior water in key roles protein hydration driving remain elusive. Here, we employ single-droplet vibrational Raman spectroscopy illuminate structural redistribution within during neuronal IDPs. Our measurements reveal changes hydrogen bonding network homotypic heterotypic governed by various molecular drivers. Such offer a potent generic tool unmask intriguing sequence-encoded interactions governing macromolecular into membraneless organelles, synthetic condensates, protocells.

Язык: Английский

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Protein interactions, calcium, phosphorylation, and cholesterol modulate CFTR cluster formation on membranes

Proceedings of the National Academy of Sciences, Год журнала: 2025, Номер 122(11)

Опубликована: Март 10, 2025

The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel whose dysfunction leads to intracellular accumulation of ions, dehydration cell surfaces, and subsequent damage airway ductal organs. Beyond its function as channel, interactions between CFTR, epithelium sodium solute carrier (SLC) transporter family membrane proteins cytoplasmic proteins, including calmodulin Na+/H+ exchanger regulatory factor-1 (NHERF-1), coregulate ion homeostasis. CFTR has also been observed form mesoscale clusters. However, the contributions multivalent protein lipid cluster formation are not well understood. Using combination computational modeling biochemical reconstitution assays, we demonstrate that with binding partners, calcium, cholesterol can induce on model membranes. Phosphorylation domains promotes in absence indicating multiple mechanisms contribute formation. Our findings reveal coupling consistent membrane-associated biological phase separation.

Язык: Английский

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Simple visualization of submicroscopic protein clusters with a phase-separation-based fluorescent reporter

Cell Systems, Год журнала: 2024, Номер 15(2), С. 166 - 179.e7

Опубликована: Фев. 1, 2024

Язык: Английский

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Protein conformation and biomolecular condensates

Current Research in Structural Biology, Год журнала: 2022, Номер 4, С. 285 - 307

Опубликована: Янв. 1, 2022

Protein conformation and cell compartmentalization are fundamental concepts subjects of vast scientific endeavors. In the last two decades, we have witnessed exciting advances that unveiled conjunction these concepts. An avalanche studies highlighted central role biomolecular condensates in membraneless subcellular permits spatiotemporal organization regulation myriads simultaneous biochemical reactions macromolecular interactions. These also shown condensation, driven by multivalent intermolecular interactions, is mediated order-disorder transitions protein domain architecture. Conceptually, condensation a distinct level conformational landscape which collective folding large collections molecules takes place. Biomolecular arise physical process phase separation comprise variety bodies ranging from organelles to liquid solid-like conglomerates, spanning lengths mesoscopic clusters (nanometers) micrometer-sized objects. this review, summarize discuss recent work on assembly, composition, conformation, material properties, thermodynamics, regulation, functions bodies. We review conceptual framework for future dynamics condensed proteins cellular processes.

Язык: Английский

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Proteolethargy is a pathogenic mechanism in chronic disease

Cell, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 1, 2024

Язык: Английский

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Dynamic structure of the cytoplasm

Current Opinion in Cell Biology, Год журнала: 2025, Номер 94, С. 102507 - 102507

Опубликована: Апрель 6, 2025

The cytoplasm is a dense and complex milieu in which plethora of biochemical reactions occur. Its structure not understood so far, albeit being central to cellular functioning. In this review, we highlight novel perspective the physical properties are regulated space time actively contribute function. Furthermore, underscore recent findings that dynamic formation local assemblies within cytoplasm, such as condensates polysomes, serves key regulator mesoscale cytoplasmic dynamics.

Язык: Английский

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Thermal aggregation of immunoglobulin G depending on the charge state of protein–polyelectrolyte complexes

International Journal of Biological Macromolecules, Год журнала: 2025, Номер unknown, С. 139500 - 139500

Опубликована: Янв. 1, 2025

Язык: Английский

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Solution NMR goes big: Atomic resolution studies of protein components of molecular machines and phase-separated condensates

Current Opinion in Structural Biology, Год журнала: 2025, Номер 90, С. 102976 - 102976

Опубликована: Янв. 20, 2025

Язык: Английский

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Functional Biomaterials Derived from Protein Liquid–Liquid Phase Separation and Liquid‐to‐Solid Transition

Advanced Materials, Год журнала: 2025, Номер unknown

Опубликована: Фев. 9, 2025

Protein phase transitions play a vital role in both cellular functions and pathogenesis. Dispersed proteins can undergo liquid-liquid separation to form condensates, process that is reversible highly regulated within cells. The formation physicochemical properties of these such as composition, viscosity, multiphase miscibility, are precisely modulated fulfill specific biological functions. However, protein condensates further liquid-to-solid state, forming β-sheet-rich aggregates may disrupt function lead diseases. While this phenomenon crucial for processes has significant implications neurodegenerative diseases, the behavior naturally derived or engineered polypeptides also presents opportunities developing high-performance, multifunctional materials at various scales. Additionally, unique molecular recruitment capabilities inspire innovative advancements biomaterial design applications drug discovery, delivery, biosynthesis. This work highlights recent progress understanding mechanisms underlying behavior, particularly how it responds internal changes external physical stimuli. Furthermore, fabrication from diverse sources through controlled demonstrated.

Язык: Английский

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