bioRxiv : the preprint server for biology最新文献_第7页

Hypoxia-induced metastatic heterogeneity in pancreatic cancer. 胰腺癌缺氧诱导的转移异质性。

bioRxiv : the preprint server for biology Pub Date : 2025-08-29 DOI: 10.1101/2025.08.26.672389

Pradeep Moon Gunasekaran, Qianqian Wang, Yoke-Chen Chang, Polina Guseva, Rajika Chauhan, Alexander Kley, Gene Lee, Siddharth Ghosh Roy, Yousef Masoudpoor, Arthur Roberts, Kelly Watkins Walton, Lucyann Franciosa, Shafiq Bhat, Emmanuel Zachariah, Kishan Patel, Zhongren Zhou, Wenjin Chen, Julie Zhouli Ni, Sam Guoping Gu, Cristina Montagna, Shin-Heng Chiou

{"title":"Hypoxia-induced metastatic heterogeneity in pancreatic cancer.","authors":"Pradeep Moon Gunasekaran, Qianqian Wang, Yoke-Chen Chang, Polina Guseva, Rajika Chauhan, Alexander Kley, Gene Lee, Siddharth Ghosh Roy, Yousef Masoudpoor, Arthur Roberts, Kelly Watkins Walton, Lucyann Franciosa, Shafiq Bhat, Emmanuel Zachariah, Kishan Patel, Zhongren Zhou, Wenjin Chen, Julie Zhouli Ni, Sam Guoping Gu, Cristina Montagna, Shin-Heng Chiou","doi":"10.1101/2025.08.26.672389","DOIUrl":"10.1101/2025.08.26.672389","url":null,"abstract":"In most solid tumors, hypoxia constitutes a defining microenvironmental feature that reprograms malignant cells into a highly metastatic state by driving cellular plasticity and exacerbating chromosomal instability (CIN). However, the mechanisms by which cancer cells concurrently co-opt these elements of hypoxic adaptation to promote metastasis remains poorly understood. Here, we report that hypoxia promotes metastasis by suppressing the JmjC-containing histone lysine demethylase Kdm8. CRISPR/Cas9-mediated targeting of Kdm8 in a Kras;Trp53-driven mouse model of pancreatic ductal adenocarcinoma (PDA) robustly rewires the malignant cell transcriptomic programs, leading to a profound loss of the epithelial morphology and widespread metastatic disease. In PDA patients, a high KDM8-induced gene signature is associated with reduced metastatic burden and better survival in advanced disease. Notably, Kdm8 suppression in normoxia recapitulates key aspects of the global epigenetic and transcriptomic rewiring, mitotic spindle defects, and CIN induced by hypoxia. Moreover, disruption of Kdm8's demethylase activity phenocopies Kdm8 loss, whereas expression of hypermorphic Kdm8 variants resistant to hypoxic suppression markedly reduces metastasis beyond the levels achieved by the wildtype protein. Through the suppression of Kdm8 demethylase function, hypoxia unleashes a potent metastatic program by simultaneously advancing cellular plasticity and CIN.","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12407890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145002501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Vibrio cholerae adhesin-derived peptide mediates strong pull-off forces in aqueous high-ionic-strength environments. 霍乱弧菌黏附素衍生肽在高离子强度的水环境中介导强牵引力。

bioRxiv : the preprint server for biology Pub Date : 2025-08-29 DOI: 10.1101/2025.08.25.672170

Syeda Tajin Ahmed, Sixin Zhai, Xin Huang, Sarvagya Sulaja, Adekunle Adewole, Alisa Ioffe, Andrea D Merg, Jing Yan, Roberto C Andresen Eguiluz

{"title":"Vibrio cholerae adhesin-derived peptide mediates strong pull-off forces in aqueous high-ionic-strength environments.","authors":"Syeda Tajin Ahmed, Sixin Zhai, Xin Huang, Sarvagya Sulaja, Adekunle Adewole, Alisa Ioffe, Andrea D Merg, Jing Yan, Roberto C Andresen Eguiluz","doi":"10.1101/2025.08.25.672170","DOIUrl":"10.1101/2025.08.25.672170","url":null,"abstract":"In this letter, the pull-off forces of adsorbed films of four Bap1-inspired peptides in various solvents were investigated on negatively charged mica substrates using the surface forces apparatus (SFA), complemented with dynamic light scattering (DLS) for characterizing the aggregation behavior of peptides in solution. Bap1-inspired peptides consisted of the 57 amino acid wild-type sequence (WT); a scrambled version of the WT used to investigate the impact of the primary amino acid sequence in pull-off forces (Scr); a ten amino acid sequence rich in hydrophobic content (CP) of the WT sequence, and an eight amino acid sequence (Sh1) that corresponds to the pseudo-repeating sequence in the 57 AA. SFA results showed remarkable pull-off forces for CP, particularly in the presence of salts: measured pull-off forces were 26.0 ± 7.0 mN/m for no dwell-time and up to 42.0 ± 8.8 mN/m when surfaces were left in contact for 30 minutes. DLS observations indicate that salts favor large peptide aggregation for all constructs ( H z > 1 µm), as compared to milliQ ( H z ≈ 100-500 nm) water and DMSO ( H z ≈ 100 nm), resulting in heterogeneous peptide film thicknesses. This letter concludes with a comparison to the pull-off forces of mussel foot protein-inspired peptides reported in the literature.","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12407685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145002485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Higher baseline alpha power is associated with faster responses in visual search. 更高的基线阿尔法能量与视觉搜索中更快的反应有关。

bioRxiv : the preprint server for biology Pub Date : 2025-08-29 DOI: 10.1101/2025.08.29.673162

Katharina Duecker, Kimron L Shapiro, Simon Hanslmayr, Benjamin J Griffiths, Andrew J Quinn, Jeremy Wolfe, Yali Pan, Aleksandra Pastuszak, Ole Jensen

{"title":"Higher baseline alpha power is associated with faster responses in visual search.","authors":"Katharina Duecker, Kimron L Shapiro, Simon Hanslmayr, Benjamin J Griffiths, Andrew J Quinn, Jeremy Wolfe, Yali Pan, Aleksandra Pastuszak, Ole Jensen","doi":"10.1101/2025.08.29.673162","DOIUrl":"10.1101/2025.08.29.673162","url":null,"abstract":"Visual search models have long emphasised that task-relevant items must be prioritized for optimal performance. While it is known that search efficiency also benefits from active distractor inhibition, the underlying neuronal mechanisms are debated. Neuronal alpha oscillations (7-14 Hz) have been associated with functional inhibition of cortical excitability, as well as distractor suppression in spatial attention and visual working memory tasks. We therefore hypothesised that alpha oscillations similarly support the deselection of distractors in visual search. Using Magnetoencephalography (MEG), we here show that high alpha power before the onset of a complex search display is associated with faster search performance. Crucially, we used a General Linear Model (GLM) approach to control for confounds between alpha power and task duration, ruling out that this result was merely driven by practice effects paired with increased fatigue over time. In addition to spontaneous oscillatory activity, we quantified the cortical excitability to colours of the search stimuli based on Rapid Invisible Frequency Tagging (RIFT) responses. In contrast to our initial hypothesis, increased pre-search alpha power did not correlate with the RIFT response, providing no direct evidence for feature-specific inhibition of distracting stimuli by alpha. Our findings challenge the traditional view of alpha oscillations reducing visual processing, showing instead that increased occipital alpha power can enhance performance in a visual task. We propose that the increase in alpha power may reflect increased top-down control supporting visual search.","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12407961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145002555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Discovery of homoharringtonine pathway enzymes reveals a whole plant model for coordinated biosynthesis. 同源杉碱途径酶的发现揭示了整个植物协调生物合成的模式。

bioRxiv : the preprint server for biology Pub Date : 2025-08-29 DOI: 10.1101/2025.08.26.672243

Yaereen Dho, Kevin Smith, Elizabeth S Sattely

{"title":"Discovery of homoharringtonine pathway enzymes reveals a whole plant model for coordinated biosynthesis.","authors":"Yaereen Dho, Kevin Smith, Elizabeth S Sattely","doi":"10.1101/2025.08.26.672243","DOIUrl":"10.1101/2025.08.26.672243","url":null,"abstract":"Plants have evolved to produce diverse molecules that inhibit protein translation. A lead example is homoharringtonine (HHT), both a key tool for ribosomal profiling and an FDA-approved treatment for chronic myeloid leukemia. HHT is commercially produced through semi-synthesis by esterifying the alkaloid core cephalotaxine (CET) extracted from endangered Cephalotaxus species. Despite its medicinal significance, a biosynthetic pathway to CET and HHT has not been described. Here, we use paired untargeted metabolomics (stable-isotope labeled precursor feeding) and transcriptomics to elucidate a near-complete biosynthesis to CET without prior knowledge of intermediates and biosynthetic genes. We show that while CET alkaloid core is actively biosynthesized only in growing root tips, both CET and HHT accumulate throughout the plant. We discovered and characterized seven CET pathway intermediates and six novel biosynthetic enzymes that, together, can be used to produce cephalotaxinone, the likely direct precursor of CET. Included are non-canonical cytochrome P450s, an atypical short-chain dehydrogenase, and a 2-oxogluatrate-dependent dioxygenase that together result in carbon excision and the formation of the characteristic pentacyclic backbone of HHT alkaloids. Our data support a model where cephalotaxinone is the last pathway intermediate produced specifically in the root tips, and its distribution throughout the plant is likely the starting point for subsequent elaboration to HHT. This study not only establishes a metabolic route to the core scaffold of HHT-enabling future sustainable, large-scale production of this valuable drug-but also suggests how Cephalotaxus species employ a whole plant coordination to regulate the biosynthesis of eukaryotic ribosomal toxins.","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12407900/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145002571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Advancing Luciferase Activity and Stability beyond Directed Evolution and Rational Design through Expert Guided Deep Learning. 通过专家引导深度学习推进荧光素酶活性和稳定性，超越定向进化和理性设计。

bioRxiv : the preprint server for biology Pub Date : 2025-08-29 DOI: 10.1101/2025.08.25.672183

Spencer Gardiner, Joseph Talley, Christopher Haynie, Joshua Ebbert, Corbyn Kubalek, Matthew Argyle, Deon Allen, William Heaps, Tyler Green, Dallin Chipman, Bradley C Bundy, Dennis Della Corte

{"title":"Advancing Luciferase Activity and Stability beyond Directed Evolution and Rational Design through Expert Guided Deep Learning.","authors":"Spencer Gardiner, Joseph Talley, Christopher Haynie, Joshua Ebbert, Corbyn Kubalek, Matthew Argyle, Deon Allen, William Heaps, Tyler Green, Dallin Chipman, Bradley C Bundy, Dennis Della Corte","doi":"10.1101/2025.08.25.672183","DOIUrl":"https://doi.org/10.1101/2025.08.25.672183","url":null,"abstract":"Engineered luciferases have transformed biological imaging and sensing, yet optimizing NanoLuc luciferase (NLuc) remains challenging due to the inherent stability-activity trade-off and its limited sequence homology with characterized proteins. We report a hybrid approach that synergistically integrates computational deep learning with structure-guided rational design to develop enhanced NLuc variants that improve thermostability and thereby activity at elevated temperatures. By systematically analyzing libraries of engineered variants, we established that modifications to termini and loops distal from the catalytic center, combined with preservation of allosterically coupled networks, effectively enhance thermal resilience while maintaining enzymatic function. Our optimized variants - notably B.07 and B.09 - exhibit substantial thermostability enhancements (increases of 4.2 °C and 5.2 °C at 50 % solubility), leading to increased activity at elevated temperatures (320 % and 370 % of wild-type at 55 °C). These variants maintain NLuc's pH tolerance and retain improved activity with the alternative substrate coelenterazine. Molecular dynamics simulations and protein folding studies elucidate how these mutations favorably modulate conformational landscapes without perturbing substrate binding architecture. Beyond providing superior tools for bioluminescence applications, our integrated methodology establishes a broadly applicable framework for engineering enzymes where traditional homology-based approaches fail, and stability-activity constraints present formidable barriers to improvement.","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12407786/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145002434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

One-pot cloning and protein expression platform for genetic engineering. 一锅克隆及基因工程蛋白表达平台。

bioRxiv : the preprint server for biology Pub Date : 2025-08-29 DOI: 10.1101/2025.08.28.672974

Wakana Sato, Judee Sharon, Brock Cash, Christopher Deich, Nathaniel J Gaut, Joseph Heili, Aaron E Engelhart, Katarzyna P Adamala

引用次数: 0

Electrical Oscillations in Microtubules. 微管中的电振荡。

bioRxiv : the preprint server for biology Pub Date : 2025-08-29 DOI: 10.1101/2025.08.25.672199

Md Mohsin, Horacio Cantiello, María Del Rocío Cantero, Marcelo Marucho

{"title":"Electrical Oscillations in Microtubules.","authors":"Md Mohsin, Horacio Cantiello, María Del Rocío Cantero, Marcelo Marucho","doi":"10.1101/2025.08.25.672199","DOIUrl":"10.1101/2025.08.25.672199","url":null,"abstract":"Environmental perturbations and local changes in cellular electric potential can stimulate cytoskeletal filaments to transmit ionic currents along their surface. Advanced models and accurate experiments may provide a molecular understanding of these processes and reveal their role in cell electrical activities. This article introduces a multi-scale electrokinetic model incorporating atomistic protein details and biological environments to characterize electrical impulses along microtubules. We consider that condensed ionic layers on microtubule surfaces form two coupled asymmetric nonlinear electrical transmission lines. The model accounts for tubulin-tubulin interactions, dissipation, and a nanopore coupling between inner and outer surfaces, enabling luminal currents, energy transfer, amplification, and oscillatory dynamics that resemble the experimentally observed transistor properties of microtubules. The approach has been used to analyze how different electrolyte conditions and voltage stimuli affect electrical impulses' shape, attenuation, oscillation, and propagation velocity along microtubules. Integrating transistor-like properties in the microtubules model has profound implications for intracellular communication and bioelectronic applications.","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12407702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145002552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Temporal dynamics of cytokine, leukocyte, and whole blood transcriptome profiles of pigs infected with African swine fever virus. 感染非洲猪瘟病毒的猪的细胞因子、白细胞和全血转录组谱的时间动态。

bioRxiv : the preprint server for biology Pub Date : 2025-08-29 DOI: 10.1101/2025.08.29.673161

Daniel W Madden, Bianca Libanori Artiaga, Jessie D Trujillo, Patricia Assato, Chester D McDowell, Isaac Fitz, Taeyong Kwon, Konner Cool, Yonghai Li, Natasha N Gaudreault, Igor Morozov, Juergen A Richt

{"title":"Temporal dynamics of cytokine, leukocyte, and whole blood transcriptome profiles of pigs infected with African swine fever virus.","authors":"Daniel W Madden, Bianca Libanori Artiaga, Jessie D Trujillo, Patricia Assato, Chester D McDowell, Isaac Fitz, Taeyong Kwon, Konner Cool, Yonghai Li, Natasha N Gaudreault, Igor Morozov, Juergen A Richt","doi":"10.1101/2025.08.29.673161","DOIUrl":"10.1101/2025.08.29.673161","url":null,"abstract":"African swine fever virus (ASFV) is an important transboundary animal pathogen with significant impacts on the global swine industry. Overwhelming proinflammatory responses are a major virulence mechanism for ASFV, but the dynamics of these changes during clinical disease are not completely understood. We constructed a detailed portrait of the innate immune responses during acute African swine fever (ASF) at the cellular, transcriptomic, and cytokine levels. Samples serially obtained from infected piglets show progression of acute ASF is characterized by rapid increases in plasma type I interferons, TNF-α, IL-12p40, and IL-10, which coincide with the manifestation of clinical disease and viral DNAemia. Lymphocytes and natural killer (NK) cells progressively declined, with fluctuations in B cell, CD8+ T cell, and CD4+/CD8+ T cell populations. Blood monocytes and macrophages were highly variable throughout infection, with an abrupt spike in CD203+ mature macrophages immediately prior to death. Transcriptomic analysis of blood showed downregulation of cellular translation as early as 1 day post challenge (DPC), and significant upregulation of antiviral immune processes at 5 DPC and 7 DPC which overlapped with the onset of clinical disease. Together, these results present a highly detailed delineation of fatal ASF as involving an initial infection and damage of susceptible myeloid cells prior to symptomatic disease characterized by pro-inflammatory immune responses, lymphoid depletion, and clinical deterioration.","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12407888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145002675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Stationary-Phase Pseudomonas aeruginosa Fluoroquinolone Persisters Mostly Avoid DNA Double-Stranded Breaks. 稳定期铜绿假单胞菌氟喹诺酮类药物大多避免DNA双链断裂。

bioRxiv : the preprint server for biology Pub Date : 2025-08-29 DOI: 10.1101/2025.08.29.673110

Patricia J Hare, Juliet R González, Wendy W K Mok

{"title":"Stationary-Phase Pseudomonas aeruginosa Fluoroquinolone Persisters Mostly Avoid DNA Double-Stranded Breaks.","authors":"Patricia J Hare, Juliet R González, Wendy W K Mok","doi":"10.1101/2025.08.29.673110","DOIUrl":"https://doi.org/10.1101/2025.08.29.673110","url":null,"abstract":"When susceptible bacterial cultures are treated with antibiotics, some cells can survive treatment without heritable resistance, giving rise to susceptible daughter cells in a phenomenon termed antibiotic persistence. Current models of fluoroquinolone (FQ) persistence in stationary-phase cultures posit that post-treatment resuscitation is dependent on double-stranded break (DSB) repair through RecA-mediated homology-directed repair. Previously, we found that stationary-phase P. aeruginosa does not depend on RecA to persist. In this work, we ask whether P. aeruginosa FQ persisters from stationary-phase cultures require DSB repair at all. We measured DSB formation in Levofloxacin (LVX)-treated cells recovering from treatment using strains expressing fluorescently labeled DSB-binding protein, Gam. We find that, surprisingly, the majority of P. aeruginosa LVX persisters survive treatment without apparent DSBs. Persisters that have evidence of DSBs take longer until their first division compared to persisters without DSBs, and the phenotypes of their progeny suggest how persisters cope with DSBs-via repair or by damage sequestration-in order to successfully propagate. These observations pave the way for mechanistic studies into P. aeruginosa FQ persistence and highlight the need for single-cell tools to track FQ-induced damage.","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12407917/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Functional diversity of Arabidopsis late embryogenesis abundant proteins in response to changes in the physicochemical environment. 拟南芥胚胎发生晚期功能多样性丰富蛋白响应物化环境变化。

bioRxiv : the preprint server for biology Pub Date : 2025-08-29 DOI: 10.1101/2025.08.26.672499

L D Palomino-Navarrete, D Pérez-Villanueva, D Moses, E Gollub, K Nguyen, S Sanchez-Martinez, F Yu, K Martinez, T C Boothby, S Sukenik, C L Cuevas-Velazquez

{"title":"Functional diversity of Arabidopsis late embryogenesis abundant proteins in response to changes in the physicochemical environment.","authors":"L D Palomino-Navarrete, D Pérez-Villanueva, D Moses, E Gollub, K Nguyen, S Sanchez-Martinez, F Yu, K Martinez, T C Boothby, S Sukenik, C L Cuevas-Velazquez","doi":"10.1101/2025.08.26.672499","DOIUrl":"10.1101/2025.08.26.672499","url":null,"abstract":"Some desiccation-tolerant organisms accumulate intrinsically disordered proteins (IDPs), such as Late Embryogenesis Abundant (LEA) proteins, which help protect other proteins from inactivation and/or aggregation during desiccation. Like other IDPs, LEA proteins adopt ensembles of extended conformations that shift in response to environmental changes. Desiccation causes dramatic changes in the cellular environment, but it is unclear how the structural malleability of LEAs is related to their protective function. In this work, we measured the in vitro protective function and structural sensitivity to changes in the environment of four Arabidopsis thaliana LEA proteins from different families. We found that all LEAs showed different protection efficiencies of the labile enzyme lactate dehydrogenase under desiccation in vitro. In line with this, we identified distinct ensemble structural changes when these LEA proteins were exposed to different physicochemical environments. Specifically, AtEM1, AtLEA7, and AtLEA4-5 showed compaction when the solution was crowded with polymers, whereas AtLEA6-2.2 showed larger structural changes when salt concentrations were increased. Furthermore, the ensembles of AtEM1, AtLEA7, and AtLEA4-5 gained helicity under desiccated conditions, while that of AtLEA6-2.2 remained largely disordered. Our results highlight how ensemble properties of LEA proteins contribute to their distinct functional activities in vitro. This work advances our understanding of the molecular features that contribute to functional diversity in desiccation-related IDPs.","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12407985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145002518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0