Biology subjects

Diaz-Moreno, I.

Publications and source records attributed to Diaz-Moreno, I..

6 recordsLinked to original sources

bioRxiv2026

Acetylation facilitates NPM1 anchoring in the nucleolus by boosting liquid-liquid phase separation

Nucleophosmin (NPM1) is a multifunctional nucleolar protein whose integration into the nucleolus relies on multivalent interactions that drive liquid-liquid phase separation (LLPS). Acetylation of Lys27 and Lys54 within the N-terminal oligomerization domain of NPM1 has been implicated in its nucleolar redistribution during the DNA damage response, but the molecular mechanisms underlying this redistribution remain unclear. Here, we show that Lys27/Lys54 acetylation facilitates NPM1 anchoring in the nucleolus under basal conditions by promoting LLPS. Despite preserving NPM1 structural integrity and oligomerization equilibrium, lysine acetylation reshapes the electrostatic surface potential of the N-terminal domain, neutralizing a predominantly basic region and exposing a previously cryptic acidic surface. This increased charge blockiness enhances the ability of NPM1 to undergo both homotypic and heterotypic LLPS. Thus, lysine acetylation acts as a modulator of NPM1 interaction landscape, promoting its integration into nucleolar condensates despite not constituting the primary determinant of its localization.

biochemistry↗

bioRxiv2026

Human NLRP1 and NLRP3 interact driving inflammation in inflammosomopathies and inflammatory diseases

Inflammasomes are multiprotein complexes that form and activate after exposure to pathogenic microbes and host danger signals that trigger an inflammatory response. Although NLRP1 and NLRP3 inflammasomes share structural similarities and can be activated by similar stimuli, no evidence of heterotypic inflammasome assemblies has been reported. Here, we identify a unique interaction between NLRP1 and NLRP3 in human cells, forming a hybrid inflammasome, to drive inflammation. NLRP1 is essential for this hydrid inflammasome activation and NLRP3-mediated Caspase-1 activation and release of IL-1{beta} and IL-18. The presence of the heterocomplex inflammasome was confirmed in blood samples from patients after kidney transplantation and is associated with inflammatory responses driven by NLRP3 and MEFV mutations that cause inflammasomopathies. Our findings reveal an unexpected level of intricacy in inflammasome composition, pinpointing hybrid targets that may pave the way for innovative pharmacological treatments for inflammatory disorders. Significance StatementPrevious findings showed interactions between NLRP3 and NLRC4 or NLRP3 and NLRP11 showing that would be possible the interaction of the inflammasomes as supercomplexes and not working alone. Now, we show a new inflammasome heterocomplex inflammasome between NLRP1 and NLRP3 which is associated to the inflammatory profile in autoimmune diseases patietns and transplanted patients. These findings could open a new research topic for the design of dual inflammasomes inhibitors.

immunology↗

bioRxiv2025

Allosteric modulation of TIA-1 phase separation by double serine phosphorylation

In response to diverse harmful stimuli, eukaryotic cells generate cytoplasmic stress granules (SGs), mainly composed of mRNAs and RNA-binding proteins (RBPs). RBPs are fine-tuned by a diverse array of post-translational modifications (PTMs), with important consequences for the assembly, dynamics and clearance of SGs. One of the best characterized SG nucleators is the RBP T-cell intracellular antigen 1 (TIA-1), although knowledge about the structural and functional impact of its identified PTMs is very limited. TIA-1 is organized into three RNA-recognition motifs (RRMs) and a C-terminal prion-related domain (PRD) that drives its phase separation from the cytosol. Here, we analyzed the effect of TIA-1 double phosphorylation in RRM3, at serines 198 and 199. Microscopic observations revealed an increased propensity of the phosphomimetic TIA-1 S198/199E to undergo liquid-liquid phase separation (LLPS) and self-assemble into SGs independently of stress stimuli. Our computational simulations, supported by NMR data, have suggested that such phosphorylations promote the formation of a {beta}-hairpin motif at the beginning of the PRD. Moreover, the ALS-associated mutation V283M in TIA-1 was predicted to lead to the formation of an aberrant structure in the {beta}-hairpin region, highlighting the fine balance between physiological and pathogenic TIA-1 phase transition, and the importance of a better understanding of the molecular mechanisms underlying the liquid demixing of this RBP.

biophysics↗

bioRxiv2024

NMR based metabolomic workflow to unravel the molecular mechanisms involved in strawberry vernalization

Metabolomics is the discipline that aims to determine the whole metabolic profile of a complex mixture. These studies are useful to capture the physiological status of an organism at a given moment. Even though the main technique used in metabolomics is Mass Spectrometry coupled to chromatography, in recent years, interest in Nuclear Magnetic Resonance (NMR) is increasing because of some benefits of NMR, i.e., it is a non-invasive, highly reproducible, and inherently quantitative technique. However, difficulties in data analysis comprise one of the main reasons that hinder the standardization of NMR for metabolomic analysis in research. In this work, we applied an automated workflow for NMR-based metabolomic analysis for the study of vernalization in strawberry. Vernalization is a key process in obtaining a successful strawberry crop, however, the molecular mechanisms behind it remain still unknown. We expect this work to improve the knowledge of crop metabolism --specifically the vernalization process-- while promoting the use of NMR in conjunction with computational tools for agriculture studies.

biochemistry↗

bioRxiv2022

Histone chaperones exhibit conserved functionality in nucleosome remodeling

Chromatin homeostasis mediates some of the most fundamental processes in the eukaryotic cell. In this regard, histone chaperones have emerged as major regulatory factors during DNA replication, repair, and transcription. However, the dynamic nature of these processes has severely impeded their characterization at the molecular level. Here we apply single-molecule probing by fluorescence optical tweezers to follow histone chaperone dynamics in real-time. The molecular action of SET/template-activating factor-I{beta} and nucleophosmin 1--representing the two most common histone chaperone folds--were examined using both nucleosomes and isolated core histones. We show that these chaperones present binding specificity for partially dismantled nucleosomes and are able to recognize and disrupt non-native histone-DNA interactions. Furthermore, we reveal that cytochrome c inhibition of histone chaperones is coupled to chaperone accumulation on DNA-bound histones. Our single-molecule approach shows that despite the drastically different structures of these chaperones, they present conserved modes of action mediating nucleosome remodeling.

biophysics↗

bioRxiv2020

Mitochondrial cytochrome c liberates the nucleophosmin-sequestered ARF tumor suppressor in the nucleolus

The alternative reading frame (ARF) protein is crucial in the cellular response to oncogenic stress, being likewise the second most frequently inactivated gene in a wide spectrum of human cancers. ARF is usually sequestered in the nucleolus by the well-known oncogenic nucleophosmin (NPM) protein and is liberated in response to cell damage to exhibit its tumor-suppressor ability. However, the mechanism underlying ARF activation is unknown. Here we show that mitochondria-to-nucleus translocation of cytochrome c upon DNA damage leads to the break-off of the NPM-ARF ensemble and subsequent release of ARF from the nucleoli. Our structural and subcellular data support a molecular model in which the hemeprotein triggers the extended-to-compact conformation of NPM and competes with ARF for binding to NPM.

biophysics↗