Molecules and Cells最新文献_第5页

Brief guide to immunostaining 免疫染色简要指南。

IF 3.7 3区生物学

Molecules and Cells Pub Date : 2025-01-01 DOI: 10.1016/j.mocell.2024.100157

Gyutae Park , Sieun S. Kim , Jiwon Shim , Seung-Jae V. Lee

引用次数: 0

Biological functions and molecular mechanisms of MORC2 in human diseases MORC2在人类疾病中的生物学功能和分子机制。

IF 3.7 3区生物学

Molecules and Cells Pub Date : 2025-01-01 DOI: 10.1016/j.mocell.2024.100166

Xin Zhao , Jinfeng Miao

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Crystal structure of γ-carbonic anhydrase from the polyextremophilic bacterium Aeribacillus pallidus 多嗜极细菌苍白气杆菌γ-碳酸酐酶的晶体结构。

IF 3.7 3区生物学

Molecules and Cells Pub Date : 2025-01-01 DOI: 10.1016/j.mocell.2024.100165

Seung Hun Choi, Mi Sun Jin

{"title":"Crystal structure of γ-carbonic anhydrase from the polyextremophilic bacterium Aeribacillus pallidus","authors":"Seung Hun Choi, Mi Sun Jin","doi":"10.1016/j.mocell.2024.100165","DOIUrl":"10.1016/j.mocell.2024.100165","url":null,"abstract":"<div><div>The polyextremophilic bacterium <em>Aeribacillus pallidus</em> produces a thermo- and alkali-stable γ-carbonic anhydrase (γ-apCA), a homotrimeric metalloenzyme containing a zinc ion in its active site that catalyzes the reversible hydration of carbon dioxide (CO<sub>2</sub>). Here, we present the first crystal structure of γ-apCA at 1.7-Å resolution, revealing 2 trimers in the asymmetric unit. The overall structure is consistent with other γ-CAs, where each monomer adopts a prism-like structure consisting of an N-terminal left-handed β-helix and a C-terminal α-helix. The active site, located at the interface between 2 monomers, coordinates the zinc ion with 3 histidine residues (H65, H82, and H87) and a water molecule in a tetrahedral configuration. The structural comparison indicates that the amino acid composition at the active site of γ-apCA differs significantly from the prototypic γ-CA from <em>Methanosarcina thermophila</em>. This variation likely accounts for the lack of measurable CO<sub>2</sub> hydration activity in γ-apCA. Additionally, the structure reveals noncatalytic zinc and sulfate ions trapped at the trimer core and trimer-trimer noncrystallographic interfaces. These may contribute to stabilizing enzyme assembly and promoting crystal packing.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"48 1","pages":"Article 100165"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11721427/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142786167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pentraxin 3 deficiency ameliorates streptozotocin-induced pancreatic toxicity via regulating ER stress and β-cell apoptosis 戊曲霉素3缺乏通过调节内质网应激和β细胞凋亡改善链脲佐菌素诱导的胰腺毒性。

IF 3.7 3区生物学

Molecules and Cells Pub Date : 2025-01-01 DOI: 10.1016/j.mocell.2024.100168

Suji Kim , Ae-Rang Hwang , Sun-Hee Kim , Jae Hyang Lim , Chang-Hoon Woo

{"title":"Pentraxin 3 deficiency ameliorates streptozotocin-induced pancreatic toxicity via regulating ER stress and β-cell apoptosis","authors":"Suji Kim , Ae-Rang Hwang , Sun-Hee Kim , Jae Hyang Lim , Chang-Hoon Woo","doi":"10.1016/j.mocell.2024.100168","DOIUrl":"10.1016/j.mocell.2024.100168","url":null,"abstract":"<div><div>The long pentraxin 3 (PTX3), a marker of inflammation, has been associated with cardiovascular disease, obesity, and metabolic syndrome. Recently, elevated serum PTX3 levels have been linked to type 2 diabetes in obese patients with nonalcoholic fatty liver disease. Diabetes mellitus is a metabolic syndrome characterized by hyperglycemia resulting from insufficient insulin secretion or action. However, the precise role of PTX3 in hyperglycemia remains unclear. This study aimed to investigate the physiological roles of PTX3 in vivo. The deformation of pancreatic islets was mitigated in PTX3-deficient mice treated with streptozotocin (STZ) compared to control C57BL/6J mice. In addition, PTX3 deficiency prevented STZ-induced unfolded protein responses and pancreatic β-cell death. Immunoblotting data revealed significant inhibition of inositol-requiring protein1α and C/EBP homologous protein (CHOP) protein expression in PTX3 KO mice administered tunicamycin which is a chemical endoplasmic reticulum stress inducer. Similarly, tunicamycin-induced Grp78, Grp94, ATF6, and CHOP mRNA levels were reduced in PTX3 KO mice. Moreover, recombinant PTX3–induced CHOP expression and β-cell apoptosis in primary mouse islets. These findings suggest that PTX3 plays a critical role in STZ-induced deformation of pancreatic islets via regulating endoplasmic reticulum stress and β-cell apoptosis.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"48 1","pages":"Article 100168"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The disordered effector RipAO of Ralstonia solanacearum destabilizes microtubule networks in Nicotiana benthamiana cells 烟碱菌的紊乱效应物RipAO破坏了烟碱细胞的微管网络。

IF 3.7 3区生物学

Molecules and Cells Pub Date : 2025-01-01 DOI: 10.1016/j.mocell.2024.100167

Hyelim Jeon , Wanhui Kim , Cécile Segonzac

{"title":"The disordered effector RipAO of Ralstonia solanacearum destabilizes microtubule networks in Nicotiana benthamiana cells","authors":"Hyelim Jeon , Wanhui Kim , Cécile Segonzac","doi":"10.1016/j.mocell.2024.100167","DOIUrl":"10.1016/j.mocell.2024.100167","url":null,"abstract":"<div><div><em>Ralstonia solanacearum</em> causes bacterial wilt, a devastating disease in solanaceous crops. The pathogenicity of <em>R. solanacearum</em> depends on its type III secretion system, which delivers a suite of type III effectors into plant cells. The disordered core effector RipAO is conserved across <em>R. solanacearum</em> species and affects plant immune responses when transiently expressed in <em>Nicotiana benthamiana</em>. Specifically, RipAO impairs pathogen-associated molecular pattern–triggered reactive oxygen species production, an essential plant defense mechanism. RipAO fused to yellow fluorescent protein initially localizes to filamentous structures, resembling the cytoskeleton, before forming large punctate aggregates around the nucleus. Consistent with these findings, tubulin alpha 6 (TUA6) and tubulin beta-1, building blocks of microtubules, were identified as putative targets of RipAO in immunoprecipitation and mass spectrometry analyses. In the presence of RipAO, TUA6-labeled microtubules fragmented into puncta, mimicking the effects of oryzalin, a microtubule polymerization inhibitor. These effects were corroborated in a <em>N. benthamiana</em> transgenic line constitutively expressing green fluorescent protein-labeled TUA6, where RipAO reduced microtubule density and stability at an accumulation level that did not induce aggregation. Moreover, oryzalin treatment further enhanced RipAO’s impairment of reactive oxygen species production, suggesting that RipAO disrupts microtubule networks via its association with tubulins, leading to immune suppression. Further research into RipAO’s interaction with the microtubule network will enhance our understanding of bacterial strategies to subvert plant immunity.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"48 1","pages":"Article 100167"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11730531/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

STK33 as the functional substrate of miR-454-3p for suppression and apoptosis in neuroblastoma STK33 是 miR-454-3p 抑制神经母细胞瘤并使其凋亡的功能底物。

IF 3.7 3区生物学

Molecules and Cells Pub Date : 2024-12-01 DOI: 10.1016/j.mocell.2024.100145

Dongkwan Yoo, Sichen Wu, Seunghyuk Choi, Sung-Oh Huh, Ali Sadra

{"title":"STK33 as the functional substrate of miR-454-3p for suppression and apoptosis in neuroblastoma","authors":"Dongkwan Yoo, Sichen Wu, Seunghyuk Choi, Sung-Oh Huh, Ali Sadra","doi":"10.1016/j.mocell.2024.100145","DOIUrl":"10.1016/j.mocell.2024.100145","url":null,"abstract":"<div><div>miR-454-3p has been reported to be a tumor-suppressive microRNA (miRNA) in multiple cancer types. We identified the kinase STK33 mRNA, which is a high-risk factor for survival in neuroblastoma (NB) patients, as being a substrate of miR-454-3p in NB. Even though STK33 is an attractive target for several cancers, the development of inhibitors of STK33 has been challenging. For the various cell lines tested, we demonstrated reduced growth and viability with the miR-454-3p mimic. From among the candidate NB-associated miRNAs, miR-454-3p mimic and its antagonist had the most profound effect on STK33 mRNA and protein-level changes. Under various conditions of growth and external stress for the cells, the RNA levels for miR-454-3p and STK33 also negatively correlated. Luciferase reporter assays demonstrated STK33 as a substrate for miR-454-3p, and recombinant versions of STK33 resistant to miR-454-3p significantly blunted the suppressive effect of the miR-454-3p and established STK33 as the major functional substrate of miR-454-3p. Overexpression of miR-454-3p or knockdown of STK33 mRNA promoted autophagy and at the same time, increased the apoptotic markers in the tested NB cells, indicating a mechanism for the suppressive effect of the agents. Given the difficult-to-drug targets such as STK33 and the recent successes in RNA delivery methods for cancer treatment, it is thought that targeting cancer cells with a suppressive miRNA such as miR-454-3p for STK33-dependent cancer types may be an alternative means of NB therapy.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"47 12","pages":"Article 100145"},"PeriodicalIF":3.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Single-molecule FRET–based approach for protein-targeted drug discovery 基于单分子 FRET 的蛋白质靶向药物发现方法。

IF 3.7 3区生物学

Molecules and Cells Pub Date : 2024-12-01 DOI: 10.1016/j.mocell.2024.100150

Yuyoung Kim , Surim Kim , Kang Heo , Sanghwa Lee

{"title":"Single-molecule FRET–based approach for protein-targeted drug discovery","authors":"Yuyoung Kim , Surim Kim , Kang Heo , Sanghwa Lee","doi":"10.1016/j.mocell.2024.100150","DOIUrl":"10.1016/j.mocell.2024.100150","url":null,"abstract":"<div><div>Many therapeutic drugs target various proteins involved in diverse biological processes. Among these proteins, type II topoisomerases are critical targets for anticancer and antibacterial chemotherapies, yet the action mechanisms of many type II topoisomerase-targeting drugs have not been fully elucidated. In this regard, the development of rapid and accurate methods to identify the mode of action of potential drug candidates is crucial to improve the efficiency of drug screening and discovery. Here, using type II topoisomerase as a model system, we present a single-molecule fluorescence resonance energy transfer–based drug screening method capable of delineating when and how the drug candidates participate in the entire reaction steps of the target protein. This unique capability has been demonstrated to be applicable to the identification of representative types of widely prescribed drugs targeting type II topoisomerase: etoposide which stabilizes the enzyme-DNA cleavage complex, and bisdioxopiperazines (ICRF-I93) which lock the N-terminal gate of the enzyme into the closed state. Based on this demonstration experiment, we expect that our proposed method will be extended to broad applications in the screening of potent drugs targeting various proteins.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"47 12","pages":"Article 100150"},"PeriodicalIF":3.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11667156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dipeptidyl peptidase 4 as an injury-responsive protein in the mouse sciatic nerve 二肽基肽酶 4 是小鼠坐骨神经的损伤反应蛋白。

IF 3.7 3区生物学

Molecules and Cells Pub Date : 2024-12-01 DOI: 10.1016/j.mocell.2024.100159

Yeonsoo Oh, Yongcheol Cho

引用次数: 0

Nα-terminal acetylation meets ferroptosis via N-degron pathway Nα-末端乙酰化通过 N-去甲肾上腺素途径与铁凋亡相遇

IF 3.7 3区生物学

Molecules and Cells Pub Date : 2024-12-01 DOI: 10.1016/j.mocell.2024.100160

Jihye Yang , Cheol-Sang Hwang

引用次数: 0

PKA regulates autophagy through lipolysis during fasting PKA 在禁食期间通过脂肪分解调节自噬作用

IF 3.7 3区生物学

Molecules and Cells Pub Date : 2024-12-01 DOI: 10.1016/j.mocell.2024.100149

Yul Ji , Yong Geun Jeon , Won Taek Lee , Ji Seul Han , Kyung Cheul Shin , Jin Young Huh , Jae Bum Kim

{"title":"PKA regulates autophagy through lipolysis during fasting","authors":"Yul Ji , Yong Geun Jeon , Won Taek Lee , Ji Seul Han , Kyung Cheul Shin , Jin Young Huh , Jae Bum Kim","doi":"10.1016/j.mocell.2024.100149","DOIUrl":"10.1016/j.mocell.2024.100149","url":null,"abstract":"<div><div>Autophagy is a crucial intracellular degradation process that provides energy and supports nutrient deprivation adaptation. However, the mechanisms by which these cells detect lipid scarcity and regulate autophagy are poorly understood. In this study, we demonstrate that protein kinase A (PKA)-dependent lipolysis delays autophagy initiation during short-term nutrient deprivation by inhibiting AMP-activated protein kinase (AMPK). Using coherent anti-Stokes Raman spectroscopy, we visualized free fatty acids (FFAs) in vivo and observed that lipolysis-derived FFAs were used before the onset of autophagy. Our data suggest that autophagy is triggered when the supply of FFAs is insufficient to meet energy demands. Furthermore, PKA activation promotes lipolysis and suppresses AMPK-driven autophagy during early fasting. Disruption of this regulatory axis impairs motility and reduces the lifespan of <em>Caenorhabditis elegans</em> during fasting. These findings establish PKA as a critical regulator of catabolic pathways, prioritizing lipolysis over autophagy by modulating AMPK activity to prevent premature autophagic degradation during transient nutrient deprivation.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"47 12","pages":"Article 100149"},"PeriodicalIF":3.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11697058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0