Biochimica et biophysica acta. Molecular cell research最新文献_第2页

Editorial for the BBA-MCR Special Issue on "Biogenesis and Function Iron-sulfur Proteins". BBA-MCR 特刊 "铁硫蛋白的生物生成和功能 "编辑。

IF 4.6 2区生物学

Biochimica et biophysica acta. Molecular cell research Pub Date : 2024-10-24 DOI: 10.1016/j.bbamcr.2024.119867

Roland Lill, Frederic Barras

引用次数: 0

Involvement of aquaporins in Shiga toxin-induced swelling and water transport dysfunction in human renal microvascular endothelial cells 水蒸发蛋白参与滋贺毒素诱导的人肾微血管内皮细胞肿胀和水转运功能障碍。

IF 4.6 2区生物学

Biochimica et biophysica acta. Molecular cell research Pub Date : 2024-10-21 DOI: 10.1016/j.bbamcr.2024.119866

Fernando D. Gomez , Julieta Reppetti , Romina S. Alvarez , Daniel C. Girón Reyes , Flavia Sacerdoti , Alejandro Balestracci , Alicia E. Damiano , Nora A. Martínez , Gisela Di Giusto , María M. Amaral

{"title":"Involvement of aquaporins in Shiga toxin-induced swelling and water transport dysfunction in human renal microvascular endothelial cells","authors":"Fernando D. Gomez , Julieta Reppetti , Romina S. Alvarez , Daniel C. Girón Reyes , Flavia Sacerdoti , Alejandro Balestracci , Alicia E. Damiano , Nora A. Martínez , Gisela Di Giusto , María M. Amaral","doi":"10.1016/j.bbamcr.2024.119866","DOIUrl":"10.1016/j.bbamcr.2024.119866","url":null,"abstract":"<div><div>One of the hallmarks of Shiga toxin-producing <em>Escherichia coli</em>-associated hemolytic uremic syndrome (STEC-HUS) is kidney damage. Our previous research demonstrated that Shiga toxin type 2 (Stx2a) decreases cell viability and induces swelling of human glomerular endothelial cells (HGEC). However, Stx2a can disrupt net water transport across HGEC monolayers without affecting cell viability. This work aimed to elucidate the possible mechanisms involved in the water transport disruption caused by Stx2a across HGEC monolayers. We investigated paracellular and transcellular water transfer across HGEC by analyzing the passage of FITC-Dextran and the hydrostatic pressure (Phydr) and measuring the osmotic pressure (Posm), respectively. Stx2a selectively affected the transcellular pathway without impacting the paracellular route. Furthermore, Stx2a cell swelling was prevented by pretreatment with aquaporin inhibitors tetraethylammonium chloride (TEA), Mercury (II) chloride (HgCl<sub>2</sub>) or TGN-020, suggesting aquaporin involvement in this process. Confocal microscopy revealed that Stx2a increased HGEC total volume, which TEA and TGN-020 counteracted. Additionally, we identified in HGEC not only the expression of aquaporin-1 (AQP1) but also the expression of aquaporin-4 (AQP4). Surprisingly, we observed a decrease in the expression of both AQPs after Stx2a exposure. Our findings suggest that Stx2a may induce water movement into HGEC via AQP1 and AQP4, increasing total cell volume. Subsequently, decreased AQP1 and AQP4 expression could inhibit transcellular water transfer, potentially as a protective mechanism against excessive water entry and cell lysis.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 1","pages":"Article 119866"},"PeriodicalIF":4.6,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Synergy of native mass spectrometry and other biophysical techniques in studies of iron‑sulfur cluster proteins and their assembly 本机质谱和其他生物物理技术在铁硫簇蛋白质及其组装研究中的协同作用。

IF 4.6 2区生物学

Biochimica et biophysica acta. Molecular cell research Pub Date : 2024-10-21 DOI: 10.1016/j.bbamcr.2024.119865

Jason C. Crack, Nick E. Le Brun

{"title":"Synergy of native mass spectrometry and other biophysical techniques in studies of iron‑sulfur cluster proteins and their assembly","authors":"Jason C. Crack, Nick E. Le Brun","doi":"10.1016/j.bbamcr.2024.119865","DOIUrl":"10.1016/j.bbamcr.2024.119865","url":null,"abstract":"<div><div>The application of mass spectrometric methodologies has revolutionised biological chemistry, from identification through to structural and conformational studies of proteins and other macromolecules. Native mass spectrometry (MS), in which proteins retain their native structure, is a rapidly growing field. This is particularly the case for studies of metalloproteins, where non-covalently bound cofactors remain bound following ionisation. Such metalloproteins include those that contain an iron‑sulfur (Fe<img>S) cluster and, despite their fragility and O<sub>2</sub> sensitivity, they have been a particular focus for applications of native MS because of its capacity to accurately monitor mass changes that reveal chemical changes at the cluster. Here we review recent advances in these applications of native MS, which, together with data from more traditionally applied biophysical methods, have yielded a remarkable breadth of information about the Fe<img>S species present, and provided key mechanistic insight not only for Fe<img>S cluster proteins themselves, but also their assembly.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 1","pages":"Article 119865"},"PeriodicalIF":4.6,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

IL-17A's role in exacerbating radiation-induced lung injury: Autophagy impairment via the PP2A-mTOR pathway IL-17A 在加剧辐射诱导的肺损伤中的作用：通过 PP2A-mTOR 通路的自噬损伤

IF 4.6 2区生物学

Biochimica et biophysica acta. Molecular cell research Pub Date : 2024-10-20 DOI: 10.1016/j.bbamcr.2024.119864

Liangzhong Liu , GuangMing Yi , Xiaohong Li , Cai Chen , Kehong Chen , Hengqiu He , Jinjin Li , Fanghao Cai , Yuan Peng , Zhenzhou Yang , Xiaoyue Zhang

{"title":"IL-17A's role in exacerbating radiation-induced lung injury: Autophagy impairment via the PP2A-mTOR pathway","authors":"Liangzhong Liu , GuangMing Yi , Xiaohong Li , Cai Chen , Kehong Chen , Hengqiu He , Jinjin Li , Fanghao Cai , Yuan Peng , Zhenzhou Yang , Xiaoyue Zhang","doi":"10.1016/j.bbamcr.2024.119864","DOIUrl":"10.1016/j.bbamcr.2024.119864","url":null,"abstract":"<div><h3>Objective</h3><div>Radiation-induced lung injury (RILI) is a serious complication of radiotherapy, and the role of IL-17A in this process is not well understood. While IL-17A has been shown to modulate autophagy, conflicting reports exist regarding its activation or inhibition of autophagy. This study investigates the role of IL-17A in RILI and its effects on autophagy via the PP2A-mTOR pathway, with a focus on the PP2A B56α subunit.</div></div><div><h3>Methods</h3><div>C57BL/6J mice and human lung epithelial cells (BEAS-2B) were exposed to radiation with or without recombinant IL-17A. Autophagy markers were analyzed using Western blotting, immunofluorescence, and autophagy flux assays. PP2A activity, specifically the B56α subunit, was measured. A PP2A agonist (DT-061) was used to verify its role in reversing IL-17A-mediated autophagy inhibition.</div></div><div><h3>Results</h3><div>IL-17A inhibited autophagy in lung epithelial cells exposed to radiation by suppressing PP2A activity, particularly through downregulation of the B56α subunit, leading to mTOR activation and reduced autophagosome formation. Treatment with DT-061 restored autophagic activity and improved cell viability. These findings align with reports suggesting that IL-17A inhibits autophagy in certain contexts, while other studies have shown opposing effects.</div></div><div><h3>Conclusion</h3><div>IL-17A inhibits autophagy in RILI through the PP2A B56α-mTOR pathway, exacerbating lung damage. Further research is needed to clarify the role of IL-17A in different cell types and conditions. Targeting the IL-17A-PP2A B56α-mTOR axis may offer new therapeutic strategies for RILI management.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 1","pages":"Article 119864"},"PeriodicalIF":4.6,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mitoception, or transfer of normal cell mitochondria to cancer cells, reverses remodeling of store-operated Ca2+ entry in tumor cells 线粒体接收，或将正常细胞线粒体转移到癌细胞中，可逆转肿瘤细胞中储存操作的 Ca2+ 进入的重塑。

IF 4.6 2区生物学

Biochimica et biophysica acta. Molecular cell research Pub Date : 2024-10-20 DOI: 10.1016/j.bbamcr.2024.119862

Verónica Feijóo , Sendoa Tajada , Alejandra Méndez-Mena , Lucía Núñez , Carlos Villalobos

{"title":"Mitoception, or transfer of normal cell mitochondria to cancer cells, reverses remodeling of store-operated Ca2+ entry in tumor cells","authors":"Verónica Feijóo , Sendoa Tajada , Alejandra Méndez-Mena , Lucía Núñez , Carlos Villalobos","doi":"10.1016/j.bbamcr.2024.119862","DOIUrl":"10.1016/j.bbamcr.2024.119862","url":null,"abstract":"<div><div>Most cancer cells show the Warburg effect, the rewiring of aerobic metabolism to glycolysis due to defective mitochondrial ATP synthesis. As a consequence, tumor cells display enhanced mitochondrial potential (∆Ψ), the driving force for mitochondrial Ca<sup>2+</sup> uptake. Mitochondria control the Ca<sup>2+</sup>-dependent inactivation of store-operated channels (SOCs), leading to enhanced and sustained store-operated Ca<sup>2+</sup> entry (SOCE) involved in cancer hallmarks. We asked here whether the transfer of mitochondria (mitoception) from normal cells to tumor cells may reverse SOCE remodeling in cancer cells. For this end, we labeled mitochondria in normal NCM460 human colonic cells, isolated them and transferred them to tumor HT29 cells. We tested the viability and efficiency of mitoception using flow cytometry and confocal microscopy, as well as calcium imaging to investigate the effects of mitoception on SOCE. Our results show that mitoception of tumor HT29 cells with normal mitochondria restores a low ∆Ψ and SOCE. Conversely, self-mitoception of tumor HT29 cells with tumor cell mitochondria increases further ∆Ψ and SOCE, thus excluding the possibility that effects of mitoception are due to increased mitochondrial mass. Strikingly, mitoception of normal NCM460 cells with tumor cell mitochondria has no effects on either ∆Ψ or SOCE. These results are consistent with the previous proposal that transformed mitochondria may modulate SOC channels involved in SOCE. Further research is warranted to test whether mitoception of cancer cells with normal mitochondria may reverse Ca<sup>2+</sup> remodeling associated to cancer.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 1","pages":"Article 119862"},"PeriodicalIF":4.6,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Interleukin-2 receptor α (IL-2Rα/CD25) shedding is differentially regulated by N- and O-glycosylation 白细胞介素-2受体α（IL-2Rα/CD25）脱落受N-和O-糖基化的不同调节。

IF 4.6 2区生物学

Biochimica et biophysica acta. Molecular cell research Pub Date : 2024-10-19 DOI: 10.1016/j.bbamcr.2024.119863

Amelie Franke , Sophia Dahl , Monika Funck , Hans Bakker , Christoph Garbers , Juliane Lokau

{"title":"Interleukin-2 receptor α (IL-2Rα/CD25) shedding is differentially regulated by N- and O-glycosylation","authors":"Amelie Franke , Sophia Dahl , Monika Funck , Hans Bakker , Christoph Garbers , Juliane Lokau","doi":"10.1016/j.bbamcr.2024.119863","DOIUrl":"10.1016/j.bbamcr.2024.119863","url":null,"abstract":"<div><div>The cytokine interleukin-2 (IL-2) is a critical regulator of immune responses, with an especially well-characterized role in regulating T-cell homeostasis. IL-2 signaling involves three distinct receptor subunits: the IL-2Rα (CD25), IL-2Rβ, and IL-2Rγ. The intracellular transduction of IL-2-induced signals is strictly dependent on IL-2Rβ and IL-2Rγ, while the IL-2Rα is not directly involved in signaling. Instead, it has the highest affinity towards IL-2 and is thus responsible for regulating the affinity of a cell for IL-2. In addition to the membrane-bound IL-2Rα, a soluble form of the receptor (sIL-2Rα) has been described, which is present in the blood of healthy individuals, increased under various pathological conditions, and able to bind IL-2 and thus modulate its function. The sIL-2Rα is generated by proteolytic cleavage of the membrane-bound receptor. Here, we analyze whether glycosylation of the IL-2Rα regulates its proteolysis. We find that constitutive IL-2Rα shedding is affected by glycosylation and discover distinct roles for N- and O-glycosylation. Furthermore, we show that induced shedding by the metalloproteases ADAM10 and ADAM17 is also differentially regulated by distinct types of glycans. Finally, we identify a specific role for an N-glycan at an exosite in ADAM17-mediated proteolysis that does not affect ADAM10, indicating distinct substrate recognition mechanisms. These results further the understanding of the mechanisms leading to sIL-2Rα generation, and thus offer the opportunity to specifically modulate the generation of the soluble receptor.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 1","pages":"Article 119863"},"PeriodicalIF":4.6,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142456977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 special issue of the ECS2022 meeting in Cork, Ireland. 在爱尔兰科克举行的 ECS2022 会议特刊。

IF 4.6 2区生物学

Biochimica et biophysica acta. Molecular cell research Pub Date : 2024-10-10 DOI: 10.1016/j.bbamcr.2024.119861

Geert Bultynck, Björn-Philipp Diercks, Enikö Kallay, John Mackrill

引用次数: 0

USP7 facilitates deubiquitination of LRRC42 in colorectal cancer to accelerate tumorigenesis and augment Wnt/β-catenin signaling USP7 在结直肠癌中促进 LRRC42 的去泛素化，从而加速肿瘤发生并增强 Wnt/β-catenin 信号传导。

IF 4.6 2区生物学

Biochimica et biophysica acta. Molecular cell research Pub Date : 2024-10-09 DOI: 10.1016/j.bbamcr.2024.119859

Yunze Li , Xin Sun , Zhe Huang

{"title":"USP7 facilitates deubiquitination of LRRC42 in colorectal cancer to accelerate tumorigenesis and augment Wnt/β-catenin signaling","authors":"Yunze Li , Xin Sun , Zhe Huang","doi":"10.1016/j.bbamcr.2024.119859","DOIUrl":"10.1016/j.bbamcr.2024.119859","url":null,"abstract":"<div><div>Colorectal cancer is a prevalent malignancy with an increasing incidence worldwide. Leucine-rich repeat-containing protein 42 (LRRC42) is known to be dysregulated in tumor tissues, yet its role in colorectal cancer remains largely unexplored. Herein, the function of LRRC42 in colorectal cancer was investigated using clinical samples, cellular experiments, animal models, and multiple omics techniques. The results demonstrated that LRRC42 was highly expressed in colorectal cancer tissues and was associated with poor clinical outcomes. Silencing LRRC42 suppressed cell proliferation, induced G0/G1 phase arrest, and promoted apoptosis by reducing Bcl2 expression while elevating the expression of Bax, cleaved PARP and cleaved caspase 3. Conversely, LRRC42 overexpression exhibited the opposite effects. Consistent findings were observed in vivo. Additionally, ubiquitin specific peptidase 7 was identified as a potential LRRC42-interacting protein through immunoprecipitation-mass spectrometry, with ubiquitin specific peptidase 7 stabilizing LRRC42 expression by promoting its deubiquitination. Notably, LRRC42 overexpression partially reversed the effects of ubiquitin specific peptidase 7 silencing on tumor cell proliferation and apoptosis. mRNA sequencing analysis revealed that differentially expressed genes in LRRC42 overexpressing cells were linked to Wnt signaling pathway, suggesting that LRRC42 overexpression may activate this pathway. Furthermore, LRRC42 was proved to elevate the levels of ki67, cyclin D1 and WNT3, while reducing the level of p-β-catenin. These findings suggest that LRRC42 perhaps serve as a potential oncogenic factor in colorectal cancer, regulated by ubiquitin specific peptidase 7 and capable of activating Wnt/β-catenin signaling pathway.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 1","pages":"Article 119859"},"PeriodicalIF":4.6,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142405977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Atrial natriuretic peptide (ANP) modulates stress-induced autophagy in endothelial cells 心房利钠肽（ANP）可调节内皮细胞中由压力诱导的自噬。

IF 4.6 2区生物学

Biochimica et biophysica acta. Molecular cell research Pub Date : 2024-10-09 DOI: 10.1016/j.bbamcr.2024.119860

Maurizio Forte , Simona Marchitti , Flavio di Nonno , Donatella Pietrangelo , Rosita Stanzione , Maria Cotugno , Luca D'Ambrosio , Alessandra D'Amico , Vittoria Cammisotto , Gianmarco Sarto , Erica Rocco , Beatrice Simeone , Sonia Schiavon , Daniele Vecchio , Roberto Carnevale , Salvatore Raffa , Giacomo Frati , Massimo Volpe , Sebastiano Sciarretta , Speranza Rubattu

{"title":"Atrial natriuretic peptide (ANP) modulates stress-induced autophagy in endothelial cells","authors":"Maurizio Forte , Simona Marchitti , Flavio di Nonno , Donatella Pietrangelo , Rosita Stanzione , Maria Cotugno , Luca D'Ambrosio , Alessandra D'Amico , Vittoria Cammisotto , Gianmarco Sarto , Erica Rocco , Beatrice Simeone , Sonia Schiavon , Daniele Vecchio , Roberto Carnevale , Salvatore Raffa , Giacomo Frati , Massimo Volpe , Sebastiano Sciarretta , Speranza Rubattu","doi":"10.1016/j.bbamcr.2024.119860","DOIUrl":"10.1016/j.bbamcr.2024.119860","url":null,"abstract":"<div><div>Atrial natriuretic peptide (ANP), a cardiac hormone involved in the regulation of water/sodium balance and blood pressure, is also secreted by endothelial cells, where it exerts protective effects in response to stress. Autophagy is an intracellular self-renewal process involved in the degradation of dysfunctional cytoplasmic elements. ANP was recently reported to act as an extracellular regulator of cardiac autophagy. However, its role in the regulation of endothelial autophagy has never been investigated. Here, we tested the effects of ANP in the regulation of autophagy in human umbilical vein endothelial cells (HUVECs). We found that ANP rapidly increases autophagy and autophagic flux at physiological concentrations through its predominant pathway, mediated by natriuretic peptide receptor type A (NPR-A) and protein kinase G (PKG). We further observed that ANP is rapidly secreted by HUVEC under stress conditions, where it mediates stress-induced autophagy through autocrine and paracrine mechanisms. Finally, we found that the protective effects of ANP in response to high-salt loading or tumor necrosis factor (TNF)-α are blunted by concomitant inhibition of autophagy. Overall, our results suggest that ANP acts as an endogenous autophagy activator in endothelial cells. The autophagy mechanism mediates the protective endothelial effects exerted by ANP.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 1","pages":"Article 119860"},"PeriodicalIF":4.6,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Structural analysis of microtubule binding by minus-end targeting protein Spiral2 负端靶向蛋白 Spiral2 与微管结合的结构分析

IF 4.6 2区生物学

Biochimica et biophysica acta. Molecular cell research Pub Date : 2024-10-04 DOI: 10.1016/j.bbamcr.2024.119858

Marina Ohno , Yuuki Higuchi , Kazune Yamai , Sotaro Fuchigami , Takema Sasaki , Yoshihisa Oda , Ikuko Hayashi

{"title":"Structural analysis of microtubule binding by minus-end targeting protein Spiral2","authors":"Marina Ohno , Yuuki Higuchi , Kazune Yamai , Sotaro Fuchigami , Takema Sasaki , Yoshihisa Oda , Ikuko Hayashi","doi":"10.1016/j.bbamcr.2024.119858","DOIUrl":"10.1016/j.bbamcr.2024.119858","url":null,"abstract":"<div><div>Microtubules (MTs) are dynamic cytoskeletal polymers that play a critical role in determining cell polarity and shape. In plant cells, acentrosomal MTs are localized on the cell surface and are referred to as cortical MTs. Cortical MTs nucleate in the cell cortex and detach from nucleation sites. The released MT filaments perform treadmilling, with the plus-ends of MTs polymerizing and the minus-ends depolymerizing. Minus-end targeting proteins, -TIPs, include Spiral2, which regulates the minus-end dynamics of acentrosomal MTs. Spiral2 accumulates autonomously at MT minus-ends and inhibits filament shrinkage, but the mechanism by which Spiral2 specifically recognizes minus-ends of MTs remains unknown. Here we describe the crystal structure of Spiral2's N-terminal MT-binding domain. The structural properties of this domain resemble those of the HEAT repeat structure of the tumor overexpressed gene (TOG) domain, but the number of HEAT repeats is different and the conformation is highly arched. Gel filtration and co-sedimentation analyses demonstrate that the domain binds preferentially to MT filaments rather than the tubulin dimer, and that the tubulin-binding mode of Spiral2 <em>via</em> the basic surface is similar to that of the TOG domain. We constructed an <em>in silico</em> model of the Spiral2-tubulin complex to identify residues that potentially recognize tubulin. Mutational analysis revealed that the key residues inferred in the model are involved in microtubule recognition, and provide insight into the mechanism by which end-targeting proteins stabilize MT ends.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1871 8","pages":"Article 119858"},"PeriodicalIF":4.6,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0