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Endogenous beta‐galactosidase activity marks a TREM2‐expressing Kupffer cell population in injured livers of Lgr5‐LacZ and wild‐type mice 内源性β -半乳糖苷酶活性标志着Lgr5 - LacZ和野生型小鼠损伤肝脏中表达TREM2的库普弗细胞群
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2019-11-09 DOI: 10.1002/1873-3468.13669
Mariliis Klaas, Kristina Mäemets-Allas, K. Lõhmussaar, M. Tooming, J. Viil, V. Jaks
{"title":"Endogenous beta‐galactosidase activity marks a TREM2‐expressing Kupffer cell population in injured livers of Lgr5‐LacZ and wild‐type mice","authors":"Mariliis Klaas, Kristina Mäemets-Allas, K. Lõhmussaar, M. Tooming, J. Viil, V. Jaks","doi":"10.1002/1873-3468.13669","DOIUrl":"https://doi.org/10.1002/1873-3468.13669","url":null,"abstract":"Lgr5‐LacZ mice harbor the Escherichia coli LacZ gene encoding β‐galactosidase (β‐gal) under the control of the Lgr5 promoter, a stem/progenitor cell marker. In injured livers of Lgr5‐LacZ mice, cells expressing β‐galactosidase (β‐gal) are considered as potential bipotent liver progenitors; however, their origin and identity remain unknown. Unexpectedly, using lineage tracing, we demonstrate that the β‐gal+ cells do not originate from liver parenchymal cells. Instead, β‐gal+ cells, isolated from injured livers of both Lgr5‐LacZ and wild‐type mice, are positive for markers of Kupffer cells, liver‐resident macrophages. The β‐gal expression in these cells is a result of elevated expression of the endogenous beta‐galactosidase Glb1. In injured livers of Lgr5‐LacZ mice, bacterial β‐gal expression is very low, suggesting transgene silencing. The gene expression profile of the β‐gal+ Kupffer cells from injured livers suggests a role in liver regeneration.","PeriodicalId":50454,"journal":{"name":"FEBS Letters","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2019-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/1873-3468.13669","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42999628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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: 1
Crystal structure of the catalytic D2 domain of the AAA+ ATPase p97 reveals a putative helical split‐washer‐type mechanism for substrate unfolding AAA+ atp酶p97催化D2结构域的晶体结构揭示了一种假定的螺旋分裂-洗涤-型底物展开机制
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2019-11-07 DOI: 10.1002/1873-3468.13667
L. Stach, R. Morgan, Linda Makhlouf, A. Douangamath, F. Delft, Xiaodong Zhang, P. Freemont
{"title":"Crystal structure of the catalytic D2 domain of the AAA+ ATPase p97 reveals a putative helical split‐washer‐type mechanism for substrate unfolding","authors":"L. Stach, R. Morgan, Linda Makhlouf, A. Douangamath, F. Delft, Xiaodong Zhang, P. Freemont","doi":"10.1002/1873-3468.13667","DOIUrl":"https://doi.org/10.1002/1873-3468.13667","url":null,"abstract":"Several pathologies have been associated with the AAA+ ATPase p97, an enzyme essential to protein homeostasis. Heterozygous polymorphisms in p97 have been shown to cause neurological disease, while elevated proteotoxic stress in tumours has made p97 an attractive cancer chemotherapy target. The cellular processes reliant on p97 are well described. High‐resolution structural models of its catalytic D2 domain, however, have proved elusive, as has the mechanism by which p97 converts the energy from ATP hydrolysis into mechanical force to unfold protein substrates. Here, we describe the high‐resolution structure of the p97 D2 ATPase domain. This crystal system constitutes a valuable tool for p97 inhibitor development and identifies a potentially druggable pocket in the D2 domain. In addition, its P61 symmetry suggests a mechanism for substrate unfolding by p97.","PeriodicalId":50454,"journal":{"name":"FEBS Letters","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2019-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/1873-3468.13667","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46738700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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: 6
The lysosomal membrane protein LAMP‐2 is dispensable for PINK1/Parkin‐mediated mitophagy 溶酶体膜蛋白LAMP‐2对于PINK1/Parkin介导的有丝分裂是必不可少的
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2019-11-06 DOI: 10.1002/1873-3468.13663
Xuemei Liu, Xinyi Liao, Xiyun Rao, Bin Wang, Jun Zhang, Ge Xu, Xuejun Jiang, Xia Qin, Chengzhi Chen, Zhen Zou
{"title":"The lysosomal membrane protein LAMP‐2 is dispensable for PINK1/Parkin‐mediated mitophagy","authors":"Xuemei Liu, Xinyi Liao, Xiyun Rao, Bin Wang, Jun Zhang, Ge Xu, Xuejun Jiang, Xia Qin, Chengzhi Chen, Zhen Zou","doi":"10.1002/1873-3468.13663","DOIUrl":"https://doi.org/10.1002/1873-3468.13663","url":null,"abstract":"Selective autophagy for the elimination of aberrant mitochondria, termed mitophagy, can be regulated by the kinase PINK1 and the ubiquitin ligase Parkin. The lysosome‐associated membrane protein 2 (LAMP‐2) plays diverse functions in non‐selective autophagy, chaperone‐mediated autophagy and selective autophagy for the degradation of RNA/DNA. In the present study, we investigated whether LAMP‐2 plays important roles during PINK1/Parkin‐mediated mitophagy. The results obtained clearly show that knockdown of LAMP‐2 does not cause defects in mitophagy in HeLa cells stably expressing Parkin, indicating that LAMP‐2 is dispensable for PINK1/Parkin‐mediated mitophagy. The present study is the first to determine the potential role of LAMP‐2 in PINK1/Parkin‐mediated mitophagy, thereby providing more insight into the sophisticated process of mitophagy.","PeriodicalId":50454,"journal":{"name":"FEBS Letters","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2019-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/1873-3468.13663","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42694106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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: 5
Two negatively charged invariant residues influence ligand binding and conformational dynamics of 14‐3‐3ζ 两个带负电荷的不变残基影响14-3ζ的配体结合和构象动力学
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2019-11-06 DOI: 10.1002/1873-3468.13662
Kruti Modi, Somavally Dalvi, Prasanna Venkatraman
{"title":"Two negatively charged invariant residues influence ligand binding and conformational dynamics of 14‐3‐3ζ","authors":"Kruti Modi, Somavally Dalvi, Prasanna Venkatraman","doi":"10.1002/1873-3468.13662","DOIUrl":"https://doi.org/10.1002/1873-3468.13662","url":null,"abstract":"14‐3‐3 proteins bind and modulate the activities of a wide variety of phosphoproteins. Crystal structures of 14‐3‐3 isoforms bound to phospholigands have identified several residues important for ligand binding. Here, we report the role of two invariant residues, D124 and E131, in peptide binding and peptide‐induced conformational changes of the binding pocket. Surprisingly, the D124A mutation abrogates peptide binding, while the E131A mutation results in a twofold increase in peptide affinity. The mutants are less stable than the wild‐type protein, and peptide binding restores native‐like stability to the E131A mutant. This reversibility is lost in the more open structure of D124A. Based on these results, we infer that E131 is a regulator of protein plasticity and D124 is the guardian of the active site geometry.","PeriodicalId":50454,"journal":{"name":"FEBS Letters","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2019-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/1873-3468.13662","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46652128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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: 5
Front Cover 封面
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2019-09-01 DOI: 10.1109/cscmp45713.2019.8976851
{"title":"Front Cover","authors":"","doi":"10.1109/cscmp45713.2019.8976851","DOIUrl":"https://doi.org/10.1109/cscmp45713.2019.8976851","url":null,"abstract":"","PeriodicalId":50454,"journal":{"name":"FEBS Letters","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1109/cscmp45713.2019.8976851","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45980616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
The diverse structural landscape of quadruplexes 四胞胎的多样结构景观
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2019-08-01 DOI: 10.1002/1873-3468.13547
H. Lightfoot, T. Hagen, N. Tatum, Jonathan Hall
{"title":"The diverse structural landscape of quadruplexes","authors":"H. Lightfoot, T. Hagen, N. Tatum, Jonathan Hall","doi":"10.1002/1873-3468.13547","DOIUrl":"https://doi.org/10.1002/1873-3468.13547","url":null,"abstract":"G‐quadruplexes are secondary structures formed in G‐rich sequences in DNA and RNA. Considerable research over the past three decades has led to in‐depth insight into these unusual structures in DNA. Since the more recent exploration into RNA G‐quadruplexes, such structures have demonstrated their in cellulo existence, function and roles in pathology. In comparison to Watson‐Crick‐based secondary structures, most G‐quadruplexes display highly redundant structural characteristics. However, numerous reports of G‐quadruplex motifs/structures with unique features (e.g. bulges, long loops, vacancy) have recently surfaced, expanding the repertoire of G‐quadruplex scaffolds. This review addresses G‐quadruplex formation and structure, including recent reports of non‐canonical G‐quadruplex structures. Improved methods of detection will likely further expand this collection of novel structures and ultimately change the face of quadruplex‐RNA targeting as a therapeutic strategy.","PeriodicalId":50454,"journal":{"name":"FEBS Letters","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2019-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/1873-3468.13547","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48565816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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: 82
Front Cover 前盖
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2019-08-01 DOI: 10.1002/1873-3468.13143
{"title":"Front Cover","authors":"","doi":"10.1002/1873-3468.13143","DOIUrl":"https://doi.org/10.1002/1873-3468.13143","url":null,"abstract":"","PeriodicalId":50454,"journal":{"name":"FEBS Letters","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2019-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/1873-3468.13143","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48092403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Crystal structure of cortisol complexed with its nanobody at pH 3.5 pH值为3.5时皮质醇与其纳米体复合物的晶体结构
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2019-07-24 DOI: 10.2210/pdb6itp/pdb
Y. Ding, L. Ding, Z. Wang, P. Zhong
{"title":"Crystal structure of cortisol complexed with its nanobody at pH 3.5","authors":"Y. Ding, L. Ding, Z. Wang, P. Zhong","doi":"10.2210/pdb6itp/pdb","DOIUrl":"https://doi.org/10.2210/pdb6itp/pdb","url":null,"abstract":"","PeriodicalId":50454,"journal":{"name":"FEBS Letters","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2019-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68200303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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: 3
Crystal structure of the catalytic domain of the Weissela oryzae botulinum like toxin 米芽孢杆菌类肉毒毒素催化区域的晶体结构
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2019-05-29 DOI: 10.2210/PDB6RIM/PDB
Sara Košenina, G. Masuyer, Sicai Zhang, M. Dong, P. Stenmark
{"title":"Crystal structure of the catalytic domain of the Weissela oryzae botulinum like toxin","authors":"Sara Košenina, G. Masuyer, Sicai Zhang, M. Dong, P. Stenmark","doi":"10.2210/PDB6RIM/PDB","DOIUrl":"https://doi.org/10.2210/PDB6RIM/PDB","url":null,"abstract":"Botulinum neurotoxins (BoNTs) are the most potent toxins known. So far, eight serotypes have been identified that all act as zinc-dependent endopeptidases targeting SNARE proteins and inhibiting the release of neurotransmitters. Recently, the first botulinum toxin-like protein was identified outside the Clostridial genus, designated BoNT/Wo in the genome of Weissella oryzae. Here, we report the 1.6 A X-ray crystal structure of the light chain of BoNT/Wo (LC/Wo). LC/Wo presents the core fold common to BoNTs but has an unusually wide, open, and negatively charged catalytic pocket, with an additional Ca2+ ion besides the zinc ion and a unique s-hairpin motif. The structural information will help establish the substrate profile of BoNT/Wo and help our understanding of how BoNT evolved. This article is protected by copyright. All rights reserved. (Less)","PeriodicalId":50454,"journal":{"name":"FEBS Letters","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2019-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43179020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Crystal structure of Azospirillum brasilense L-arabinose 1-dehydrogenase (NADP-bound form) 巴西偶氮螺旋菌l -阿拉伯糖1-脱氢酶(nadp - binding form)的晶体结构
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2019-05-15 DOI: 10.2210/PDB6JNK/PDB
Y. Watanabe, C. Iga, Seiya Watanabe
{"title":"Crystal structure of Azospirillum brasilense L-arabinose 1-dehydrogenase (NADP-bound form)","authors":"Y. Watanabe, C. Iga, Seiya Watanabe","doi":"10.2210/PDB6JNK/PDB","DOIUrl":"https://doi.org/10.2210/PDB6JNK/PDB","url":null,"abstract":"In Azospirillum brasilense, a gram-negative nitrogen-fixing bacterium, l-arabinose is converted to α-ketoglutarate through a nonphosphorylative metabolic pathway. In the first step in the pathway, l-arabinose is oxidized to l-arabino-γ-lactone by NAD(P)-dependent l-arabinose 1-dehydrogenase (AraDH) belonging to the glucose-fructose oxidoreductase/inositol dehydrogenase/rhizopine catabolism protein (Gfo/Idh/MocA) family. Here, we determined the crystal structures of apo- and NADP-bound AraDH at 1.5 and 2.2 A resolutions, respectively. A docking model of l-arabinose and NADP-bound AraDH and structure-based mutational analyses suggest that Lys91 or Asp169 serves as a catalytic base and that Glu147, His153, and Asn173 are responsible for substrate recognition. In particular, Asn173 may play a role in the discrimination between l-arabinose and d-xylose, the C4 epimer of l-arabinose.","PeriodicalId":50454,"journal":{"name":"FEBS Letters","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2019-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68200608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
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