The FEBS journal最新文献

{"title":"Msp1 and Pex19-Pex3 cooperate to achieve correct localization of Pex15 to peroxisomes.","authors":"Shunsuke Matsumoto, Yoshiki Kogure, Suzuka Ono, Tomoyuki Numata, Toshiya Endo","doi":"10.1111/febs.70132","DOIUrl":"https://doi.org/10.1111/febs.70132","url":null,"abstract":"<p><p>Yeast Msp1 is a dual-localized AAA-ATPase on the mitochondrial outer membrane (OM) and peroxisomal membrane. We previously showed that Msp1 transfers mistargeted tail-anchored (TA) proteins from mitochondria to the endoplasmic reticulum (ER) for degradation or delivery to their original destinations. However, the mechanism by which Msp1 in mitochondria and peroxisomes handles authentic peroxisomal TA proteins remains unclear. We show that newly synthesized Pex15 is targeted to peroxisomes primarily via the Pex19- and Pex3-dependent pathway. Mistargeted Pex15 on the mitochondrial OM is extracted by mitochondrial Msp1 and transferred to the ER via the guided-entry of TA proteins pathway for degradation or to peroxisomes via the Pex19-Pex3 pathway. Intriguingly, endogenous Pex15 localized in peroxisomes is also extracted from the membranes by peroxisomal Msp1 but returns to peroxisomes via the Pex19-Pex3 pathway. These results suggest that correct Pex15 localization to peroxisomes relies on not only the initial targeting by Pex19-Pex3 but also the constant re-routing by Msp1 and Pex19-Pex3.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144000986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"STIM2β is a Ca²⁺ signaling modulator for the regulation of mitotic clonal expansion and PPARG2 transcription in adipogenesis.","authors":"Su Ji Jeong, Bo-Woong Sim, Sun-Uk Kim, Chan Young Park","doi":"10.1111/febs.70118","DOIUrl":"https://doi.org/10.1111/febs.70118","url":null,"abstract":"<p><p>Intracellular Ca²⁺ is crucial in the regulation of adipocyte lipid metabolism and adipogenesis. In this study, we aimed to investigate the regulation mechanism of intracellular Ca²⁺ levels ([Ca²⁺]_i) during adipocyte differentiation. We found that the expression of stromal interaction molecule 2 beta (STIM2β), which is the inhibitor of store-operated Ca²⁺ entry (SOCE), is upregulated throughout the differentiation process. Evaluation of [Ca²⁺]_i in 3 T3-L1 and primary stromal vascular fraction (SVF) cells revealed that the basal Ca²⁺ level is downregulated after differentiation. Knockout (KO) of STIM2β in 3T3-L1 and primary SVF cells showed increased [Ca²⁺]_i, indicating the involvement of STIM2β in the regulation of [Ca²⁺]_i during adipogenesis. We further evaluated the function of STIM2β-mediated [Ca²⁺]_i in early and terminal differentiation of adipogenesis. Analysis of cell proliferation rate during mitotic clonal expansion (MCE) in wild-type and STIM2β KO 3T3-L1 cell lines revealed that a larger population of KO cells underwent G1 arrest, suggesting that reduced [Ca²⁺]_i by STIM2β induces MCE. Additionally, ablation of STIM2β increased differentiation efficiency, with more lipid accumulation and rapid transcriptional activation of adipogenic genes, especially proliferator-activator receptor γ2 (PPARG2). We found that PPARG2 transcription is regulated by store-operated calcium entry (SOCE) downstream transcription factors, confirming that increased [Ca²⁺]_i by STIM2β ablation promotes PPARG2 transcription during adipogenesis. Additionally, STIM2β KO mice showed hypertrophic adipose tissue development. Our data suggest that STIM2β-mediated [Ca²⁺]_i plays a pivotal role in the regulation of mitotic clonal expansion and PPARG2 gene activation and provides evidence that MCE is not a prerequisite process for terminal differentiation during adipogenesis.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144001013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The disease-linked R336C mutation in cystathionine β-synthase disrupts communication with the PLP cofactor, yet maintains the enzyme's overall structural integrity.","authors":"Carolina Conter, Reyes Núñez-Franco, Duaa Walid Al-Sadeq, Carmen Fernández-Rodríguez, Naroa Goikoetxea-Usandizaga, Gheyath K Nasrallah, Michail Nomikos, Maria Luz Martinez-Chantar, Alessandra Astegno, Gonzalo Jiménez-Osés, Luis Alfonso Martínez-Cruz","doi":"10.1111/febs.70116","DOIUrl":"https://doi.org/10.1111/febs.70116","url":null,"abstract":"<p><p>Cystathionine β-synthase (CBS) is a pyridoxal-phosphate (PLP)-dependent enzyme essential for the reverse transsulfuration pathway, where homocysteine and serine combine to form cystathionine, the immediate precursor of cysteine. Mutations in the CBS gene cause homocystinuria, a disorder associated with intellectual disability, multisystem complications, and reduced life expectancy. The CBS p.R336C mutation, linked to severe pyridoxine non-responsiveness, results in reduced enzyme activity, previously attributed to protein instability and weakened substrate and PLP binding. To clarify the effects of the pathological R336C mutation, we performed biochemical, biophysical, and crystallographic analyses, as well as molecular dynamics simulations. Our findings show that the R336C mutation minimally impacts the structural environment around residue 336, does not cause enzyme misfolding, and does not impair the binding of PLP or the allosteric activator S-adenosylmethionine (AdoMet) binding. Instead, the mutation induces subtle reorientations in nearby hydrophobic residues, including F185 and Y381, altering intramolecular contacts that perturb the interaction between asparagine 149 and the O3 oxygen of PLP. This alteration is known to potentially shift the tautomeric equilibrium of the PLP Schiff base from its catalytically active ketoenamine form to the inactive enolimine form, which aligns with the reduced activity of the R336C variant. Additionally, the R336C mutation disrupts intermolecular contacts between the catalytic core and Bateman module, altering the Bateman module's intrinsic mobility in the enzyme's basal state and potentially affecting the cavity opening required for catalysis. Importantly, the R336C variant retains the native enzyme's ability to assemble into polymeric chains in crystals, preserving its filament formation capacity.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144046855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ZNF224 enhances the oncogenic function of p21 via p53 and AKT pathways in melanoma.","authors":"Leandra Sepe, Umberto Candia, Dario Sasso Del Verme, Elvira Toscano, Marianna Toriello, Gaetano Sodaro, Roberta Rapuano, Simona Romano, Michela Grosso, Giovanni Paolella, Angelo Lupo, Paola Costanzo, Elena Cesaro","doi":"10.1111/febs.70114","DOIUrl":"https://doi.org/10.1111/febs.70114","url":null,"abstract":"<p><p>Expression of zinc finger protein 224 (ZNF224) is deregulated in various hematological and solid cancers, where its high protein levels correlate well with faster progression and worse prognosis due to activation of oncogenic pathways involved in promoting cell growth and survival, inhibiting apoptosis, and sustaining invasion and metastasis. In previous works, we identified ZNF224 as one of the mediators of the transforming growth factor beta (TGF-β)-induced pro-tumoral activities in melanoma. In the present study, we thoroughly investigated the molecular mechanisms underlying the oncogenic role of ZNF224 in this kind of cancer. We demonstrated that ZNF224 overexpression caused increased cell growth and reduced drug-mediated apoptosis by enhancing the dysregulated function of cyclin-dependent kinase inhibitor 1 [p21(CIP1/WAF1), also known as CDKN1A]. We provide strong evidence that ZNF224 overexpression in melanoma cell lines positively modulated p21(CIP1/WAF1) gene transcription in a p53-dependent manner and enhanced AKT-triggered p21(CIP1/WAF1) oncogenic effects through its protein cytosolic retention, inhibiting apoptosis and favoring cell proliferation. Analysis of transcriptomic data from human melanoma tissue samples confirmed a close relationship between p21(CIP1/WAF1) and ZNF224 in cells, at least as long as p53 functionality is maintained. The tumorigenic molecular mechanism involving ZNF224, identified in this study, provides new insights into understanding melanoma development and progression, breaking ground in the research for new therapeutic tools.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144061274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electrostatic potential as a reactivity scoring function in computer-assisted enzyme engineering.","authors":"Aitor Vega, Antoni Planas, Xevi Biarnés","doi":"10.1111/febs.70121","DOIUrl":"https://doi.org/10.1111/febs.70121","url":null,"abstract":"<p><p>The high catalytic efficiency of enzymes is attained, in part, by their capacity to stabilize electrostatically the transition state of the chemical reaction. High-throughput protocols for measuring this electrostatic contribution in computer-assisted enzyme design are limited. We present here an easy-to-compute metric that captures the electrostatic complementarity of the enzyme to the charge distribution of the substrate at the transition state. We demonstrate such a complementarity for a representative dataset of glycoside hydrolases, a large family of enzymes responsible for the hydrolytic cleavage of glycosidic bonds in oligosaccharides, polysaccharides, and glycoconjugates. We have implemented this metric in BindScan, a computer-based mutational analysis protocol to assist protein engineering. We demonstrate the predictive power of BindScan with this metric for two mechanistically distinct glycoside hydrolases: Spodoptera frugiperda β-glucosidase (Sfβgly, operates via protein nucleophile catalysis) and Bifidobacterium bifidum lacto-N-biosidase (BbLnbB, operates via substrate-assisted catalysis). The metric correctly predicts sequence positions sensible to the modulation of k_cat/K_M upon mutation from an experimental benchmark of 51 mutants of Sfβgly with 77% classification efficiency and identifies variants of BbLnbB with improved transglycosylation yields (up to 32%). Based on electrostatic potential and ligand affinity calculations, as implemented in BindScan, we propose a rational strategy to design glycoside hydrolase variants with improved transglycosylation efficiency for the synthesis of added-value glycoconjugates. The new reactivity metric may contribute to expanding the range of computational protocols available to assist enzyme engineering campaigns aimed at optimizing mechanistically relevant properties.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144059596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zic family member 5 promotes RIO kinase 3 expression to enhance pancreatic cancer survival.","authors":"Reiko Satow, Yuki Kashiwaba, Misaki Okao, Shin Takano, Yuna Aiga, Atsuko Yoneda, Kazuyoshi Hosomichi, Kiyoko Fukami","doi":"10.1111/febs.70125","DOIUrl":"https://doi.org/10.1111/febs.70125","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies with few effective therapies available. We previously determined the essential role of Zic family member 5 (ZIC5) in the survival of PDAC cells. In this study, we showed that targeting ZIC5 can effectively shrink PDAC tumors treated with gemcitabine in vivo and investigated the molecular mechanisms involved. When tumor-bearing mice were injected intravenously with ZIC5-targeting small interfering RNA, tumor volume was significantly reduced by gemcitabine treatment. RNA-sequencing analysis was used to identify the genes affected by ZIC5 knockdown. Among these, we selected the genes whose mRNA expression levels correlated with that of ZIC5 in pancreatic cancer and those associated with poor prognosis in patients with pancreatic cancer. Further analysis revealed that RIO kinase 3 (RIOK3) promotes PDAC cell survival, whereas ALDH3B1, PTGES, and TUFT1 contribute to gemcitabine resistance in MiaPaca-2 cells. We identified RIOK3 as a direct target gene of ZIC5 using ChIP and luciferase assays. Furthermore, stable expression of RIOK3 in PANC-1 cells reversed the reduction in cell number following ZIC5 knockdown. These findings highlight RIOK3 as a critical target of ZIC5, which is involved in survival signaling in PDAC cells.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144048937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DmdA-independent lag phase shortening in Phaeobacter inhibens bacteria under stress conditions.","authors":"Delia A Narváez-Barragán, Martin Sperfeld, Einat Segev","doi":"10.1111/febs.70128","DOIUrl":"https://doi.org/10.1111/febs.70128","url":null,"abstract":"<p><p>Bacteria can shorten their lag phase by using methyl groups from compounds like dimethylsulfoniopropionate (DMSP), which are incorporated into cellular components via the methionine cycle. However, the role of specific methionine synthases in this process is not fully understood. Using transcriptomics, genetics, and biochemical assays, we investigated methionine synthases involved in lag phase shortening in Phaeobacter inhibens. We focused on a cobalamin-dependent methionine synthase (MetH)-like complex encoded by three genes: a betaine-homocysteine S-methyltransferase (bmt), a cobalamin-binding protein (cbp), and an intermediate methyl carrier (PGA1_c16040). Expression profiling revealed transcriptional decoupling among these genes. Deleting bmt disrupted lag phase shortening in response to DMSP. Functional assays showed that Bmt can directly produce methionine from DMSP and betaine, independent of tetrahydrofolate (THF) or cobalamin. Interestingly, under stress conditions, lag phase shortening occurred even in the absence of dimethylsulfoniopropionate demethylase DmdA, the primary DMSP demethylase. Under osmotic and oxidative stress, bmt expression increased significantly in response to both DMSP and betaine, suggesting an alternative methylation route. This highlights the role of Bmt as both demethylase and a methionine synthase under stress, offering a cost-effective strategy for methyl group assimilation. Our findings reveal a novel stress-responsive pathway for methionine synthesis and demonstrate the role of Bmt in promoting bacterial adaptation by accelerating the lag phase.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144047177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adverse impact of acute Toxoplasma gondii infection on human spermatozoa.","authors":"Lisbeth Rojas-Barón, Leandro Tana-Hernandez, Mireille H Nguele Ampama, Raúl Sanchéz, Ulrich Gärtner, Florian M E Wagenlehner, Christian Preußer, Elke Pogge von Strandmann, Carlos Hermosilla, Anja Taubert, María E Francia, Zahady D Velasquez","doi":"10.1111/febs.70097","DOIUrl":"https://doi.org/10.1111/febs.70097","url":null,"abstract":"<p><p>Toxoplasma gondii is an obligate intracellular protozoan parasite that can infect virtually any nucleated cell within human and other endoderm animal tissue, including male reproductive organs. Herein, we investigate the capacity of T. gondii tachyzoites to infect and proliferate within the testes and epididymis and examine the resulting impact on human spermatozoa structure and functionality. We confirmed that T. gondii tachyzoites colonise and proliferate within the testes and epididymis, altering the tissue structural homeostasis, and causing immune cell infiltration and cellular damage. In addition to demonstrating that T. gondii remains infective within the testes and epididymis, in vitro experiments demonstrated a direct interaction between T. gondii tachyzoites and human spermatozoa. This resulted in a significant proportion of headless spermatozoa. Scanning and transmission electron microscopy revealed structural defects in spermatozoa, such as twisted tails and plasma membrane disruptions. Moreover, T. gondii tachyzoites triggered the loss of mitochondrial membrane potential (MMP) in spermatozoa without modulating reactive oxygen species (ROS) concentrations, and triggered cell death, pointing at mitochondrial dysfunction as a potential mechanism mediating spermatozoan damage. Our findings suggest that T. gondii infection can have profound implications for male fertility by directly damaging spermatozoa and altering testicular and epididymal structures. The study underscores the need for further research to elucidate the long-term impact of T. gondii on male reproductive health, particularly in the context of iatrogenic infertility. Given the widespread seroprevalence of T. gondii in the human population, our research emphasises the importance of considering parasitic infections in diagnosing and managing male infertility in the field of andrology.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144059382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The CRISPR-Cas9 knockout DDC SH-SY5Y in vitro model for AADC deficiency provides insight into the pathogenicity of R347Q and L353P variants: a cross-sectional structural and functional analysis.","authors":"Cristian Andres Carmona-Carmona, Giovanni Bisello, Rossella Franchini, Gianluigi Lunardi, Roberta Galavotti, Massimiliano Perduca, Rui P Ribeiro, Benny Danilo Belviso, Alejandro Giorgetti, Rocco Caliandro, Patricia M-J Lievens, Mariarita Bertoldi","doi":"10.1111/febs.70120","DOIUrl":"https://doi.org/10.1111/febs.70120","url":null,"abstract":"<p><p>Aromatic amino acid decarboxylase (AADC) deficiency is a severe inherited recessive neurotransmitter disorder caused by an impairment in dopamine synthesis due to the lack/modification of AADC, the enzyme converting l-dopa to dopamine. Patients exhibit severe movement disorders and neurodevelopmental delay, with a high risk of premature mortality. Given the lack of a reliable model for the disease, we developed a dopa decarboxylase knockout model using CRISPR/Cas9 technology in the SH-SY5Y neuroblastoma cell line. This model showed a deficiency in AADC protein and activity, with an altered dopamine metabolites profile (low homovanillic acid and high 3-O-methyldopa) and a modified expression of key enzymes, such as dopamine beta-hydroxylase and monoamine oxidases, which are involved in the catecholamine pathway. We then transfected the DDC-KO cells with two AADC catalytic variants, R347Q and L353P, which resulted in loss-of-function and an altered profile of dopamine metabolites. By combining several structural approaches (X-ray crystallography, molecular dynamics, small angle X-ray scattering, dynamic light scattering, and spectroscopy), we determined that both variants alter the flexibility of the structural element to which they belong, whose integrity is essential for catalysis. This change causes a mispositioning of essential residues at the active site, leading, in turn, to an unproductive external aldimine, identifying the molecular basis for the loss-of-function. Overall, the DDC-KO model recapitulates some key features of AADC deficiency, is useful to study the molecular basis of the disease, and represents an ideal system for small molecule screening regarding specific enzyme defects, paving the way for a precision therapeutic approach.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144032281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “Structural determinants of cold activity and glucose tolerance of a family 1 glycoside hydrolase (GH1) from Antarctic Marinomonas sp. ef1”","authors":"","doi":"10.1111/febs.70123","DOIUrl":"10.1111/febs.70123","url":null,"abstract":"<p>Gourlay LJ, Mangiagalli M, Moroni E, Lotti M and Nardini M (2024) Structural determinants of cold activity and glucose tolerance of a family 1 glycoside hydrolase (GH1) from Antarctic <i>Marinomonas</i> sp. ef1. <i>FEBS J</i>, 291: 2897–2917. https://doi.org/10.1111/febs.17096</p><p>During the finalisation of this article, the authors inadvertently omitted part of the Acknowledgements. This correction replaces the incomplete Acknowledgements section. The authors have checked the entire document and assert that they found no further errors.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":"292 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/febs.70123","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144061266","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}