Intrinsic Disorder and Phase Separation Coordinate Exocytosis, Motility, and Chromatin Remodeling in the Human Acrosomal Proteome DOI Creative Commons
Shivam Shukla,

Sean S. Lastorka,

Vladimir N. Uversky

и другие.

Proteomes, Год журнала: 2025, Номер 13(2), С. 16 - 16

Опубликована: Апрель 28, 2025

Intrinsic disorder refers to protein regions that lack a fixed three-dimensional structure under physiological conditions, enabling conformational plasticity. This flexibility allows for diverse functions, including transient interactions, signaling, and phase separation via disorder-to-order transitions upon binding. Our study focused on investigating the role of intrinsic liquid-liquid (LLPS) in human acrosome, sperm-specific organelle essential fertilization. Using computational prediction models, network analysis, Structural Classification Proteins (SCOP) functional assessments, Gene Ontology, we analyzed 250 proteins within acrosomal proteome. bioinformatic analysis yielded 97 with high levels (>30%) structural disorder. Further enrichment identified associations between disordered overlapping SCOP domains critical processes, vesicle trafficking, membrane fusion, enzymatic activation. Examples include PLC-like phosphodiesterase domain, t-SNARE P-domain calnexin/calreticulin. Protein-protein interaction networks revealed as hubs tightly interconnected systems, emphasizing their importance. LLPS propensity modeling determined over 30% these are high-probability drivers (>60%), underscoring dynamic compartmentalization. such myristoylated alanine-rich C-kinase substrate nuclear transition 2 exhibited both propensities A significant relationship (p < 0.0001, R² = 0.649) was observed level propensity, showing facilitating separation. Overall, findings provide insights into how contribute adaptability precision required fertilization, implications understanding disorders associated acrosome reaction.

Язык: Английский

On the Roles of Protein Intrinsic Disorder in the Origin of Life and Evolution DOI Creative Commons
Vladimir N. Uversky

Life, Год журнала: 2024, Номер 14(10), С. 1307 - 1307

Опубликована: Окт. 15, 2024

Obviously, the discussion of different factors that could have contributed to origin life and evolution is clear speculation, since there no way checking validity most related hypotheses in practice, as corresponding events not only already happened, but took place a very distant past. However, are few undisputable facts present at moment, such existence wide variety living forms abundant presence intrinsically disordered proteins (IDPs) or hybrid containing ordered domains regions (IDRs) all forms. Since it seems currently existing originated from common ancestor, their result evolution. Therefore, one ask logical question what role(s) structureless highly dynamic vastly multifunctional IDPs/IDRs might This study represents an attempt consider various ideas pertaining potential roles protein intrinsic disorder

Язык: Английский

Процитировано

4
Liaisons dangereuses: Intrinsic Disorder in Cellular Proteins Recruited to Viral Infection-Related Biocondensates DOI Open Access
Greta Bianchi, Stefania Brocca, Sonia Longhi

и другие.

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(3), С. 2151 - 2151

Опубликована: Янв. 21, 2023

Liquid-liquid phase separation (LLPS) is responsible for the formation of so-called membrane-less organelles (MLOs) that are essential spatio-temporal organization cell. Intrinsically disordered proteins (IDPs) or regions (IDRs), either alone in conjunction with nucleic acids, involved these intracellular condensates. Notably, viruses exploit LLPS at their own benefit to form viral replication compartments. Beyond giving rise biomolecular condensates, also known partition into cellular MLOs, thus raising question as whether phase-separating drivers behave clients/regulators. Here, we focus on a set eukaryotic sequestered factories colocalize within primary goal gathering organized, predicted, and experimental information proteins, which constitute promising targets innovative antiviral strategies. Using various computational approaches, thoroughly investigated disorder content inherent propensity undergo LLPS, along biological functions interactivity networks. Results show average, though varying degrees, enriched disorder, being correlated, expected, content. A trend, awaits further validation, tends emerge whereby most serve drivers, while more ordered tend instead be clients factories. In light high annotated behavior, our data co-drivers molecular condensation, foreshadowing key role scaffolding infection-related MLOs.

Язык: Английский

Процитировано

9
Intrinsic disorder may drive the interaction of PROS1 and MERTK in uveal melanoma DOI Creative Commons
Mak B. Djulbegovic, David J. Taylor Gonzalez, Michael Antonietti

и другие.

International Journal of Biological Macromolecules, Год журнала: 2023, Номер 250, С. 126027 - 126027

Опубликована: Июль 26, 2023

Язык: Английский

Процитировано

9
Intrinsic disorder in PRAME and its role in uveal melanoma DOI Creative Commons
Michael Antonietti, David J. Taylor Gonzalez, Mak B. Djulbegovic

и другие.

Cell Communication and Signaling, Год журнала: 2023, Номер 21(1)

Опубликована: Авг. 25, 2023

The PReferentially expressed Antigen in MElanoma (PRAME) protein has been shown to be an independent biomarker for increased risk of metastasis Class 1 uveal melanomas (UM). Intrinsically disordered proteins and regions (IDPs/IDPRs) are that do not have a well-defined three-dimensional structure linked neoplastic development. Our study aimed evaluate the presence intrinsic disorder PRAME role these structureless PRAME( +) UM.

Язык: Английский

Процитировано

9
Bioinformatics Analysis of Actin Interactome: Characterization of the Nuclear and Cytoplasmic Actin-Binding Proteins DOI

Yakov I. Mokin,

Olga I. Povarova, Iuliia A. Antifeeva

и другие.

The Protein Journal, Год журнала: 2024, Номер 43(4), С. 675 - 682

Опубликована: Июнь 2, 2024

Язык: Английский

Процитировано

3
Two decades of advances in sequence-based prediction of MoRFs, disorder-to-order transitioning binding regions DOI
Jiangning Song, Lukasz Kurgan

Expert Review of Proteomics, Год журнала: 2025, Номер unknown

Опубликована: Янв. 9, 2025

Introduction Molecular recognition features (MoRFs) are regions in protein sequences that undergo induced folding upon binding partner molecules. MoRFs common nature and can be predicted from based on their distinctive sequence signatures.

Язык: Английский

Процитировано

0
Unravelling intrinsically disordered and compositionally biased proteins in the cereal proteomes DOI
Mouna Choura, Vladimir N. Uversky

Biosystems, Год журнала: 2025, Номер unknown, С. 105409 - 105409

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

0
Fragile X mental retardation protein modulates translation of proteins with predicted tendencies for liquid-liquid phase separation DOI

Omar Jurado,

Marco V. José, Eugenio Frixione

и другие.

Biosystems, Год журнала: 2025, Номер unknown, С. 105405 - 105405

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

0
An Analysis of Intrinsic Protein Disorder in Antimicrobial Peptides DOI Creative Commons
Michael Antonietti,

Colin K. Kim,

Sydney Granack

и другие.

The Protein Journal, Год журнала: 2025, Номер unknown

Опубликована: Фев. 20, 2025

Antibiotic resistance, driven by the rise of pathogens like VRE and MRSA, poses a global health threat, prompting exploration antimicrobial peptides (AMPs) as alternatives to traditional antibiotics. AMPs, known for their broad-spectrum activity structural flexibility, share characteristics with intrinsically disordered proteins, which lack rigid structure play diverse roles in cellular processes. This study aims quantify intrinsic disorder liquid-liquid phase separation (LLPS) propensity advancing our understanding mechanisms potential therapeutic applications. To investigate LLPS we compared AMPs human proteome. The AMP sequences were retrieved from database (APD3), while proteome was obtained UniProt database. We analyzed amino acid composition using Composition Profiler tool assessed various predictors, including PONDR® IUPred, through Rapid Intrinsic Disorder Analysis Online (RIDAO) platform. For propensity, employed FuzDrop, FuzPred used predict context-dependent binding behaviors. Statistical analyses, such ANOVA χ2 tests, performed determine significance observed differences between two groups. over 3000 20,000 proteins composition, disorder, potential. analysis revealed distinct abundance, showing an enrichment both order-promoting disorder-promoting acids analysis, range consistently demonstrated that exhibit higher levels predicted than significant confirmed statistical tests. conducted showed had lower overall although specific subsets exhibited high Additionally, redox-dependent predictions highlighted how respond oxidative conditions, further suggesting functional divergences proteomes. CH-CDF plot occupy categories, greater proportion highly These findings underscore key molecular implications Our reveals possess significantly degree potential, distinguishing them likely contribute function adaptability, offering valuable insights developing novel strategies combat antibiotic resistance.

Язык: Английский

Процитировано

0
On subcellular distribution of the zinc finger 469 protein (ZNF469) and observed discrepancy in the localization of endogenous and overexpressed ZNF469 DOI Creative Commons
Anne Elisabeth Christensen Mellgren, Ileana Cristea, Thomas Stevenson

и другие.

FEBS Open Bio, Год журнала: 2025, Номер unknown

Опубликована: Март 29, 2025

The zinc finger 469 gene (ZNF469) is a single-exon predicted to encode protein of 3953 amino acids. Despite pathogenic ZNF469 variants being associated with Brittle Cornea Syndrome (BCS), relatively little known about beyond its participation in regulating the expression genes encoding extracellular matrix proteins. In this study, we examined and intracellular localization different cell lines. level mRNA varied from low levels HEK293 cells high HeLa primary fibroblasts. Antibodies against reacted among others approximately 400 kDa immunoblot analysis, which was mainly present insoluble fraction cytoplasm. Immunofluorescence analysis interphase showed small cytoplasmic puncta weak nuclear staining. dividing cells, antibodies recognized foci that also stained for proteasomes. transfected observed resembling speckles at midbody during mitosis. overlapping staining live imaging, liquid-like properties were recorded as they changed shape position occasionally fused each other. During stress granule formation, G3BP1. Finally, silico revealed large intrinsically disordered regions multiple complexity domains ZNF469. Our data indicate forms aggregates possibly biomolecular condensates when overexpressed. However, care must be taken analyzing distribution due discrepancy endogenous overexpressed cells.

Язык: Английский

Процитировано

0