Life Science Alliance最新文献_第8页

Dual-localized PPTC7 limits mitophagy through proximal and dynamic interactions with BNIP3 and NIX. 双重定位的 PPTC7 通过与 BNIP3 和 NIX 的近端和动态相互作用限制有丝分裂。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-07-11 Print Date: 2024-09-01 DOI: 10.26508/lsa.202402765

Lianjie Wei, Mehmet Oguz Gok, Jordyn D Svoboda, Keri-Lyn Kozul, Merima Forny, Jonathan R Friedman, Natalie M Niemi

{"title":"Dual-localized PPTC7 limits mitophagy through proximal and dynamic interactions with BNIP3 and NIX.","authors":"Lianjie Wei, Mehmet Oguz Gok, Jordyn D Svoboda, Keri-Lyn Kozul, Merima Forny, Jonathan R Friedman, Natalie M Niemi","doi":"10.26508/lsa.202402765","DOIUrl":"10.26508/lsa.202402765","url":null,"abstract":"PPTC7 is a mitochondrial-localized phosphatase that suppresses BNIP3- and NIX-mediated mitophagy, but the mechanisms underlying this regulation remain ill-defined. Here, we demonstrate that loss of PPTC7 upregulates BNIP3 and NIX post-transcriptionally and independent of HIF-1α stabilization. Loss of PPTC7 prolongs the half-life of BNIP3 and NIX while blunting their accumulation in response to proteasomal inhibition, suggesting that PPTC7 promotes the ubiquitin-mediated turnover of BNIP3 and NIX. Consistently, overexpression of PPTC7 limits the accumulation of BNIP3 and NIX protein levels, which requires an intact catalytic motif but is surprisingly independent of its targeting to mitochondria. Consistently, we find that PPTC7 is dual-localized to the outer mitochondrial membrane and the matrix. Importantly, anchoring PPTC7 to the outer mitochondrial membrane is sufficient to blunt BNIP3 and NIX accumulation, and proximity labeling and fluorescence co-localization experiments demonstrate that PPTC7 dynamically associates with BNIP3 and NIX within the native cellular environment. Collectively, these data reveal that a fraction of PPTC7 localizes to the outer mitochondrial membrane to promote the proteasomal turnover of BNIP3 and NIX, limiting basal mitophagy.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 9","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11239977/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141590690","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

Substrate diversity of NSUN enzymes and links of 5-methylcytosine to mRNA translation and turnover. NSUN 酶的底物多样性以及 5-甲基胞嘧啶与 mRNA 翻译和周转的联系。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-07-10 Print Date: 2024-09-01 DOI: 10.26508/lsa.202402613

Marco Guarnacci, Pei-Hong Zhang, Madhu Kanchi, Yu-Ting Hung, Hanrong Lin, Nikolay E Shirokikh, Li Yang, Thomas Preiss

{"title":"Substrate diversity of NSUN enzymes and links of 5-methylcytosine to mRNA translation and turnover.","authors":"Marco Guarnacci, Pei-Hong Zhang, Madhu Kanchi, Yu-Ting Hung, Hanrong Lin, Nikolay E Shirokikh, Li Yang, Thomas Preiss","doi":"10.26508/lsa.202402613","DOIUrl":"10.26508/lsa.202402613","url":null,"abstract":"Maps of the RNA modification 5-methylcytosine (m5C) often diverge markedly not only because of differences in detection methods, data depand analysis pipelines but also biological factors. We re-analysed bisulfite RNA sequencing datasets from five human cell lines and seven tissues using a coherent m5C site calling pipeline. With the resulting union list of 6,393 m5C sites, we studied site distribution, enzymology, interaction with RNA-binding proteins and molecular function. We confirmed tRNA:m5C methyltransferases NSUN2 and NSUN6 as the main mRNA m5C \"writers,\" but further showed that the rRNA:m5C methyltransferase NSUN5 can also modify mRNA. Each enzyme recognises mRNA features that strongly resemble their canonical substrates. By analysing proximity between mRNA m5C sites and footprints of RNA-binding proteins, we identified new candidates for functional interactions, including the RNA helicases DDX3X, involved in mRNA translation, and UPF1, an mRNA decay factor. We found that lack of NSUN2 in HeLa cells affected both steady-state levels of, and UPF1-binding to, target mRNAs. Our studies emphasise the emerging diversity of m5C writers and readers and their effect on mRNA function.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 9","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11235314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141580124","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

ER procollagen storage defect without coupled unfolded protein response drives precocious arthritis. ER胶原蛋白贮存缺陷和未折叠蛋白反应导致早老性关节炎。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-07-09 Print Date: 2024-09-01 DOI: 10.26508/lsa.202402842

Kathryn M Yammine, Sophia Mirda Abularach, Seo-Yeon Kim, Agata A Bikovtseva, Jinia Lilianty, Vincent L Butty, Richard P Schiavoni, John F Bateman, Shireen R Lamandé, Matthew D Shoulders

{"title":"ER procollagen storage defect without coupled unfolded protein response drives precocious arthritis.","authors":"Kathryn M Yammine, Sophia Mirda Abularach, Seo-Yeon Kim, Agata A Bikovtseva, Jinia Lilianty, Vincent L Butty, Richard P Schiavoni, John F Bateman, Shireen R Lamandé, Matthew D Shoulders","doi":"10.26508/lsa.202402842","DOIUrl":"10.26508/lsa.202402842","url":null,"abstract":"Collagenopathies are a group of clinically diverse disorders caused by defects in collagen folding and secretion. For example, mutations in the gene encoding collagen type-II, the primary collagen in cartilage, can lead to diverse chondrodysplasias. One example is the Gly1170Ser substitution in procollagen-II, which causes precocious osteoarthritis. Here, we biochemically and mechanistically characterize an induced pluripotent stem cell-based cartilage model of this disease, including both hetero- and homozygous genotypes. We show that Gly1170Ser procollagen-II is notably slow to fold and secrete. Instead, procollagen-II accumulates intracellularly, consistent with an endoplasmic reticulum (ER) storage disorder. Likely owing to the unique features of the collagen triple helix, this accumulation is not recognized by the unfolded protein response. Gly1170Ser procollagen-II interacts to a greater extent than wild-type with specific ER proteostasis network components, consistent with its slow folding. These findings provide mechanistic elucidation into the etiology of this disease. Moreover, the easily expandable cartilage model will enable rapid testing of therapeutic strategies to restore proteostasis in the collagenopathies.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 9","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11234256/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141563673","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

Distinct groups of autoantigens as drivers of ocular adnexal MALT lymphoma pathogenesis. 不同组别的自身抗原是眼附件 MALT 淋巴瘤发病机制的驱动因素。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-07-08 Print Date: 2024-09-01 DOI: 10.26508/lsa.202402841

Richard J Bende, Naomi Donner, Thera Am Wormhoudt, Anna Beentjes, Angelique Scantlebery, Marloes Grobben, Khadija Tejjani, Felicity Chandler, Reina S Sikkema, Anton W Langerak, Jeroen Ej Guikema, Carel Jm van Noesel

{"title":"Distinct groups of autoantigens as drivers of ocular adnexal MALT lymphoma pathogenesis.","authors":"Richard J Bende, Naomi Donner, Thera Am Wormhoudt, Anna Beentjes, Angelique Scantlebery, Marloes Grobben, Khadija Tejjani, Felicity Chandler, Reina S Sikkema, Anton W Langerak, Jeroen Ej Guikema, Carel Jm van Noesel","doi":"10.26508/lsa.202402841","DOIUrl":"10.26508/lsa.202402841","url":null,"abstract":"Chronic B-cell receptor signals incited by cognate antigens are believed to play a crucial role in the pathogenesis of mucosa-associated lymphoid tissue lymphomas. We have explored the immunoglobulin variable regions (IGHV) expressed by 124 ocular adnexal MALT lymphomas (OAML) and tested the in vitro reactivity of recombinant IgM derived from 23 OAMLs. Six of 124 OAMLs (5%) were found to express a high-affinity stereotyped rheumatoid factor. OAMLs have a biased IGHV4-34 usage, which confers intrinsic super auto-antigen reactivity with poly-N-acetyllactosamine (NAL) epitopes, present on cell surface glycoproteins of erythrocytes and B cells. Twenty-one OAMLs (17%) expressed IGHV4-34-encoded B-cell receptors. Five of the 23 recombinant OAML IgMs expressed IGHV4-34, four of which bound to the linear NAL i epitope expressed on B cells but not to the branched NAL I epitope on erythrocytes. One non-IGHV4-34-encoded OAML IgM was also reactive with B cells. Interestingly, three of the 23 OAML IgMs (13%) specifically reacted with proteins of U1-/U-snRNP complexes, which have been implicated as cognate-antigens in various autoimmune diseases such as systemic lupus erythematosus and mixed connective tissue disease. The findings indicate that local autoimmune reactions are instrumental in the pathogenesis of a substantial fraction of OAMLs.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 9","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11231493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141559091","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

FAT10 inhibits TRIM21 to down-regulate antiviral type-I interferon secretion. FAT10 可抑制 TRIM21，从而下调抗病毒 I 型干扰素的分泌。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-07-08 Print Date: 2024-09-01 DOI: 10.26508/lsa.202402786

Kritika Saxena, Katharina Inholz, Michael Basler, Annette Aichem

{"title":"FAT10 inhibits TRIM21 to down-regulate antiviral type-I interferon secretion.","authors":"Kritika Saxena, Katharina Inholz, Michael Basler, Annette Aichem","doi":"10.26508/lsa.202402786","DOIUrl":"10.26508/lsa.202402786","url":null,"abstract":"The ubiquitin-like modifier FAT10 is upregulated under pro-inflammatory conditions, targets its substrates for proteasomal degradation and functions as a negative regulator of the type-I IFN response. Influenza A virus infection upregulates the production of type-I IFN and the expression of the E3 ligase TRIM21, which regulates type-I IFN production in a positive feedback manner. In this study, we show that FAT10 becomes covalently conjugated to TRIM21 and that this targets TRIM21 for proteasomal degradation. We further show that the coiled-coil and PRYSPRY domains of TRIM21 and the C-terminal diglycine motif of FAT10 are important for the TRIM21-FAT10 interaction. Moreover, upon influenza A virus infection and in the presence of FAT10 the total ubiquitination of TRIM21 is reduced and our data reveal that the FAT10-mediated degradation of TRIM21 diminishes IFNβ production. Overall, this study provides strong evidence that FAT10 down-regulates the antiviral type-I IFN production by modulating additional molecules of the RIG-I signaling pathway besides the already published OTUB1. In addition, we elucidate a novel mechanism of FAT10-mediated proteasomal degradation of TRIM21 that regulates its stability.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 9","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11231494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141559092","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

Roles of Tubulin Concentration during Prometaphase and Ran-GTP during Anaphase of Caenorhabditis elegans Meiosis. 草履虫减数分裂后期管蛋白浓度和无丝分裂期 Ran-GTP 的作用

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-07-03 Print Date: 2024-09-01 DOI: 10.26508/lsa.202402884

Ting Gong, Karen L McNally, Siri Konanoor, Alma Peraza, Cynthia Bailey, Stefanie Redemann, Francis J McNally

{"title":"Roles of Tubulin Concentration during Prometaphase and Ran-GTP during Anaphase of Caenorhabditis elegans Meiosis.","authors":"Ting Gong, Karen L McNally, Siri Konanoor, Alma Peraza, Cynthia Bailey, Stefanie Redemann, Francis J McNally","doi":"10.26508/lsa.202402884","DOIUrl":"10.26508/lsa.202402884","url":null,"abstract":"In many animal species, the oocyte meiotic spindle, which is required for chromosome segregation, forms without centrosomes. In some systems, Ran-GEF on chromatin initiates spindle assembly. We found that in Caenorhabditis elegans oocytes, endogenously-tagged Ran-GEF dissociates from chromatin during spindle assembly but re-associates during meiotic anaphase. Meiotic spindle assembly occurred after auxin-induced degradation of Ran-GEF, but anaphase I was faster than controls and extrusion of the first polar body frequently failed. In search of a possible alternative pathway for spindle assembly, we found that soluble tubulin concentrates in the nuclear volume during germinal vesicle breakdown. We found that the concentration of soluble tubulin in the metaphase spindle region is enclosed by ER sheets which exclude cytoplasmic organelles including mitochondria and yolk granules. Measurement of the volume occupied by yolk granules and mitochondria indicated that volume exclusion would be sufficient to explain the concentration of tubulin in the spindle volume. We suggest that this concentration of soluble tubulin may be a redundant mechanism promoting spindle assembly near chromosomes.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 9","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11222656/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141498418","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

Repression of SMAD3 by STAT3 and c-Ski induces conventional dendritic cell differentiation. STAT3 和 c-Ski 对 SMAD3 的抑制可诱导常规树突状细胞分化。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-07-03 Print Date: 2024-09-01 DOI: 10.26508/lsa.201900581

Jeong-Hwan Yoon, Eunjin Bae, Yasuo Nagafuchi, Katsuko Sudo, Jin Soo Han, Seok Hee Park, Susumu Nakae, Tadashi Yamashita, Ji Hyeon Ju, Isao Matsumoto, Takayuki Sumida, Keiji Miyazawa, Mitsuyasu Kato, Masahiko Kuroda, In-Kyu Lee, Keishi Fujio, Mizuko Mamura

{"title":"Repression of SMAD3 by STAT3 and c-Ski induces conventional dendritic cell differentiation.","authors":"Jeong-Hwan Yoon, Eunjin Bae, Yasuo Nagafuchi, Katsuko Sudo, Jin Soo Han, Seok Hee Park, Susumu Nakae, Tadashi Yamashita, Ji Hyeon Ju, Isao Matsumoto, Takayuki Sumida, Keiji Miyazawa, Mitsuyasu Kato, Masahiko Kuroda, In-Kyu Lee, Keishi Fujio, Mizuko Mamura","doi":"10.26508/lsa.201900581","DOIUrl":"10.26508/lsa.201900581","url":null,"abstract":"A pleiotropic immunoregulatory cytokine, TGF-β, signals via the receptor-regulated SMADs: SMAD2 and SMAD3, which are constitutively expressed in normal cells. Here, we show that selective repression of SMAD3 induces cDC differentiation from the CD115+ common DC progenitor (CDP). SMAD3 was expressed in haematopoietic cells including the macrophage DC progenitor. However, SMAD3 was specifically down-regulated in CD115+ CDPs, SiglecH- pre-DCs, and cDCs, whereas SMAD2 remained constitutive. SMAD3-deficient mice showed a significant increase in cDCs, SiglecH- pre-DCs, and CD115+ CDPs compared with the littermate control. SMAD3 repressed the mRNA expression of FLT3 and the cDC-related genes: IRF4 and ID2. We found that one of the SMAD transcriptional corepressors, c-SKI, cooperated with phosphorylated STAT3 at Y705 and S727 to repress the transcription of SMAD3 to induce cDC differentiation. These data indicate that STAT3 and c-Ski induce cDC differentiation by repressing SMAD3: the repressor of the cDC-related genes during the developmental stage between the macrophage DC progenitor and CD115+ CDP.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 9","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11222659/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141498417","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

Trafficking of mitochondrial double-stranded RNA from mitochondria to the cytosol. 线粒体双链 RNA 从线粒体向细胞质的迁移。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-07-02 Print Date: 2024-09-01 DOI: 10.26508/lsa.202302396

Matthew R Krieger, Melania Abrahamian, Kevin L He, Sean Atamdede, Hesamedin Hakimjavadi, Milica Momcilovic, Dejerianne Ostrow, Simran Ds Maggo, Yik Pui Tsang, Xiaowu Gai, Guillaume F Chanfreau, David B Shackelford, Michael A Teitell, Carla M Koehler

{"title":"Trafficking of mitochondrial double-stranded RNA from mitochondria to the cytosol.","authors":"Matthew R Krieger, Melania Abrahamian, Kevin L He, Sean Atamdede, Hesamedin Hakimjavadi, Milica Momcilovic, Dejerianne Ostrow, Simran Ds Maggo, Yik Pui Tsang, Xiaowu Gai, Guillaume F Chanfreau, David B Shackelford, Michael A Teitell, Carla M Koehler","doi":"10.26508/lsa.202302396","DOIUrl":"10.26508/lsa.202302396","url":null,"abstract":"In addition to mitochondrial DNA, mitochondrial double-stranded RNA (mtdsRNA) is exported from mitochondria. However, specific channels for RNA transport have not been demonstrated. Here, we begin to characterize channel candidates for mtdsRNA export from the mitochondrial matrix to the cytosol. Down-regulation of SUV3 resulted in the accumulation of mtdsRNAs in the matrix, whereas down-regulation of PNPase resulted in the export of mtdsRNAs to the cytosol. Targeting experiments show that PNPase functions in both the intermembrane space and matrix. Strand-specific sequencing of the double-stranded RNA confirms the mitochondrial origin. Inhibiting or down-regulating outer membrane proteins VDAC1/2 and BAK/BAX or inner membrane proteins PHB1/2 strongly attenuated the export of mtdsRNAs to the cytosol. The cytosolic mtdsRNAs subsequently localized to large granules containing the stress protein TIA-1 and activated the type 1 interferon stress response pathway. Abundant mtdsRNAs were detected in a subset of non-small-cell lung cancer cell lines that were glycolytic, indicating relevance in cancer biology. Thus, we propose that mtdsRNA is a new damage-associated molecular pattern that is exported from mitochondria in a regulated manner.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 9","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11220484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141492476","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

Correction: A consensus molecular subtypes classification strategy for clinical colorectal cancer tissues. 更正：临床结直肠癌组织分子亚型分类共识策略。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-06-27 Print Date: 2024-09-01 DOI: 10.26508/lsa.202402889

Tim R de Back, Tan Wu, Pascale Jm Schafrat, Sanne Ten Hoorn, Miaomiao Tan, Lingli He, Sander R van Hooff, Jan Koster, Lisanne E Nijman, Geraldine R Vink, Inès J Beumer, Clara C Elbers, Kristiaan J Lenos, Dirkje W Sommeijer, Xin Wang, Louis Vermeulen

引用次数: 0

Structure of the human systemic RNAi defective transmembrane protein 1 (hSIDT1) reveals the conformational flexibility of its lipid binding domain. 人类系统性 RNAi 缺陷跨膜蛋白 1（hSIDT1）的结构揭示了其脂质结合域的构象灵活性。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-06-26 Print Date: 2024-09-01 DOI: 10.26508/lsa.202402624

Vikas Navratna, Arvind Kumar, Jaimin K Rana, Shyamal Mosalaganti

{"title":"Structure of the human systemic RNAi defective transmembrane protein 1 (hSIDT1) reveals the conformational flexibility of its lipid binding domain.","authors":"Vikas Navratna, Arvind Kumar, Jaimin K Rana, Shyamal Mosalaganti","doi":"10.26508/lsa.202402624","DOIUrl":"10.26508/lsa.202402624","url":null,"abstract":"In Caenorhabditis elegans, inter-cellular transport of the small non-coding RNA causing systemic RNAi is mediated by the transmembrane protein SID1, encoded by the sid1 gene in the systemic RNAi defective (sid) loci. SID1 shares structural and sequence similarity with cholesterol uptake protein 1 (CHUP1) and is classified as a member of the ChUP family. Although systemic RNAi is not an evolutionarily conserved process, the sid gene products are found across the animal kingdom, suggesting the existence of other novel gene regulatory mechanisms mediated by small non-coding RNAs. Human homologs of sid gene products-hSIDT1 and hSIDT2-mediate contact-dependent lipophilic small non-coding dsRNA transport. Here, we report the structure of recombinant human SIDT1. We find that the extra-cytosolic domain of hSIDT1 adopts a double jelly roll fold, and the transmembrane domain exists as two modules-a flexible lipid binding domain and a rigid transmembrane domain core. Our structural analyses provide insights into the inherent conformational dynamics within the lipid binding domain in ChUP family members.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 9","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11208740/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141457730","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