FEBS Journal最新文献_第10页

Cross-linking mass spectrometry reveals the structural topology of peripheral NuRD subunits relative to the core complex. 交联质谱法揭示了相对于核心复合物的外围NuRD亚基的结构拓扑结构。

IF 5.4 2区生物学

FEBS Journal Pub Date : 2021-05-01 Epub Date: 2020-12-14 DOI: 10.1111/febs.15650

Cornelia G Spruijt, Cathrin Gräwe, Simone C Kleinendorst, Marijke P A Baltissen, Michiel Vermeulen

{"title":"Cross-linking mass spectrometry reveals the structural topology of peripheral NuRD subunits relative to the core complex.","authors":"Cornelia G Spruijt, Cathrin Gräwe, Simone C Kleinendorst, Marijke P A Baltissen, Michiel Vermeulen","doi":"10.1111/febs.15650","DOIUrl":"https://doi.org/10.1111/febs.15650","url":null,"abstract":"The multi-subunit nucleosome remodeling and deacetylase (NuRD) complex consists of seven subunits, each of which comprises two or three paralogs in vertebrates. These paralogs define mutually exclusive and functionally distinct complexes. In addition, several proteins in the complex are multimeric, which complicates structural studies. Attempts to purify sufficient amounts of endogenous complex or recombinantly reconstitute the complex for structural studies have proven quite challenging. Until now, only substructures of individual domains or proteins and low-resolution densities of (partial) complexes have been reported. In this study, we comprehensively investigated the relative orientation of different subunits within the NuRD complex using multiple cross-link IP mass spectrometry (xIP-MS) experiments. Our results confirm that the core of the complex is formed by MTA, RBBP, and HDAC proteins. Assembly of a copy of MBD and GATAD2 onto this core enables binding of the peripheral CHD and CDK2AP proteins. Furthermore, our experiments reveal that not only CDK2AP1 but also CDK2AP2 interacts with the NuRD complex. This interaction requires the C terminus of CHD proteins. Our data provide a more detailed understanding of the topology of the peripheral NuRD subunits relative to the core complex. DATABASE: Proteomics data are available in the PRIDE database under the accession numbers PXD017244 and PXD017378.","PeriodicalId":12261,"journal":{"name":"FEBS Journal","volume":"288 10","pages":"3231-3245"},"PeriodicalIF":5.4,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/febs.15650","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38343238","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: 11

Temperature does matter-an additional dimension in kinase inhibitor development. 温度确实很重要——这是激酶抑制剂发展的另一个方面。

IF 5.4 2区生物学

FEBS Journal Pub Date : 2021-05-01 Epub Date: 2020-09-26 DOI: 10.1111/febs.15564

Miriam Strauch, Florian Heyd

引用次数: 2

Catalytic and lectin domains in neuraminidase A from Streptococcus pneumoniae are capable of an intermolecular assembly: Implications for biofilm formation. 来自肺炎链球菌的神经氨酸酶A的催化和凝集素结构域能够进行分子间组装:对生物膜形成的影响。

IF 5.4 2区生物学

FEBS Journal Pub Date : 2021-05-01 Epub Date: 2020-11-11 DOI: 10.1111/febs.15610

Yana Sharapova, Vytas Švedas, Dmitry Suplatov

{"title":"Catalytic and lectin domains in neuraminidase A from Streptococcus pneumoniae are capable of an intermolecular assembly: Implications for biofilm formation.","authors":"Yana Sharapova, Vytas Švedas, Dmitry Suplatov","doi":"10.1111/febs.15610","DOIUrl":"https://doi.org/10.1111/febs.15610","url":null,"abstract":"Neuraminidase A from Streptococcus pneumoniae (NanA) is a cell wall-bound modular enzyme containing one lectin and one catalytic domain. Unlike homologous NanB and NanC expressed by the same bacterium, the two domains within one NanA molecule do not form a stable interaction and are spatially separated by a 16-amino acid-long flexible linker. In this work, the ability of NanA to form intermolecular assemblies was characterized using the methods of molecular modeling and bioinformatic analysis based on crystallographic data and by bringing together previously published experimental data. It was concluded that two catalytic domains, as well as one catalytic and one lectin domain, originating from two cell wall-bound NanA molecules, can interact through a previously uncharacterized interdomain interface to form complexes stabilized by a network of intermolecular hydrogen bonds and salt bridges. Supercomputer modeling strongly indicated that artocarpin, an earlier experimentally discovered inhibitor of the pneumococcal biofilm formation, is able to bind to a site located in the catalytic domain of one NanA entity and prevent its interaction with the lectin or catalytic domain of another NanA entity, thus directly precluding the generation of intermolecular assemblies. The revealed structural adaptation is discussed as one plausible mechanism of noncatalytic participation of this potentially key pathogenicity enzyme in pneumococcal biofilm formation.","PeriodicalId":12261,"journal":{"name":"FEBS Journal","volume":"288 10","pages":"3217-3230"},"PeriodicalIF":5.4,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/febs.15610","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38531803","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: 4

How to build a well-rounded CV and get hired after your PhD. 如何打造一份全面的简历，并在博士毕业后找到工作。

IF 5.4 2区生物学

FEBS Journal Pub Date : 2021-05-01 Epub Date: 2020-12-02 DOI: 10.1111/febs.15635

Zheng-Shan Chong, Sara Clohisey

{"title":"How to build a well-rounded CV and get hired after your PhD.","authors":"Zheng-Shan Chong, Sara Clohisey","doi":"10.1111/febs.15635","DOIUrl":"https://doi.org/10.1111/febs.15635","url":null,"abstract":"Embarking on a PhD provides many opportunities for personal and professional development beyond scientific research. This instalment of the Words of Advice series aims to provide guidance and tips on harnessing these resources to build a well-rounded CV and increase your chances of getting hired after your PhD. We provide two perspectives on developing your CV to optimise career opportunities in academia and beyond. The first perspective is by Dr Zheng-Shan Chong, a post-doctoral researcher in Singapore, and focuses on the acquisition of a wide range of skills and experience that could open doors to a career outside of academia. Beyond her day job, Shan manages an article series on bioentrepreneurship and career development for Biotech Connection Singapore, which has allowed her to speak to several researchers who have successfully transitioned to non-research roles. Here, she summarises the insights gained from these conversations. This is followed by advice and tips from Dr Sara Clohisey, a post-doctoral researcher in Edinburgh who changed fields after her PhD, from Drosophila cell biology to human genetics and virology. Although not quite as dramatic as leaving academia completely, this shift prompted her to rethink her approach to writing an academic CV so that it would appeal to an employer from a different field. Sara's perspective is particularly geared towards careers in research. We hope that these unique perspectives from experienced individuals who have successfully navigated the path from graduate student to working scientist will prove useful to those who are planning their next moves after completing a PhD.","PeriodicalId":12261,"journal":{"name":"FEBS Journal","volume":"288 10","pages":"3072-3081"},"PeriodicalIF":5.4,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/febs.15635","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38681693","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: 7

Phosphatidylserine flux into mitochondria unveiled by organelle-targeted Escherichia coli phosphatidylserine synthase PssA. 细胞器靶型大肠杆菌磷脂酰丝氨酸合成酶PssA揭示了磷脂酰丝氨酸进入线粒体的通量。

IF 5.4 2区生物学

FEBS Journal Pub Date : 2021-05-01 Epub Date: 2020-12-30 DOI: 10.1111/febs.15657

Hiroya Shiino, Shiina Furuta, Rieko Kojima, Keisuke Kimura, Toshiya Endo, Yasushi Tamura

{"title":"Phosphatidylserine flux into mitochondria unveiled by organelle-targeted Escherichia coli phosphatidylserine synthase PssA.","authors":"Hiroya Shiino, Shiina Furuta, Rieko Kojima, Keisuke Kimura, Toshiya Endo, Yasushi Tamura","doi":"10.1111/febs.15657","DOIUrl":"https://doi.org/10.1111/febs.15657","url":null,"abstract":"Most phospholipids are synthesised in the endoplasmic reticulum and distributed to other cellular membranes. Although the vesicle transport contributes to the phospholipid distribution among the endomembrane system, exactly how phospholipids are transported to, from and between mitochondrial membranes remains unclear. To gain insights into phospholipid transport routes into mitochondria, we expressed the Escherichia coli phosphatidylserine (PS) synthase PssA in various membrane compartments with distinct membrane topologies in yeast cells lacking a sole PS synthase (Cho1). Interestingly, PssA could complement loss of Cho1 when targeted to the endoplasmic reticulum (ER), peroxisome, or lipid droplet membranes. Synthesised PS could be converted to phosphatidylethanolamine (PE) by Psd1, the mitochondrial PS decarboxylase, suggesting that phospholipids synthesised in the peroxisomes and low doses (LDs) can efficiently reach mitochondria. Furthermore, we found that PssA which has been integrated into the mitochondrial inner membrane (MIM) from the matrix side could partially complement the loss of Cho1. The PS synthesised in the MIM was also converted to PE, indicating that PS flops across the MIM to become PE. These findings expand our understanding of the intracellular phospholipid transport routes via mitochondria.","PeriodicalId":12261,"journal":{"name":"FEBS Journal","volume":"288 10","pages":"3285-3299"},"PeriodicalIF":5.4,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/febs.15657","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38681691","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: 3

Architecture of the multi-functional SAGA complex and the molecular mechanism of holding TBP. 多功能SAGA复合物的结构及保持TBP的分子机制。

IF 5.4 2区生物学

FEBS Journal Pub Date : 2021-05-01 Epub Date: 2020-09-29 DOI: 10.1111/febs.15563

Adam Ben-Shem, Gabor Papai, Patrick Schultz

{"title":"Architecture of the multi-functional SAGA complex and the molecular mechanism of holding TBP.","authors":"Adam Ben-Shem, Gabor Papai, Patrick Schultz","doi":"10.1111/febs.15563","DOIUrl":"https://doi.org/10.1111/febs.15563","url":null,"abstract":"In eukaryotes, transcription of protein encoding genes is initiated by the controlled deposition of the TATA-box binding protein TBP onto gene promoters, followed by the ordered assembly of a pre-initiation complex. The SAGA co-activator is a 19-subunit complex that stimulates transcription by the action of two chromatin-modifying enzymatic modules, a transcription activator binding module, and by delivering TBP. Recent cryo electron microscopy structures of yeast SAGA with bound nucleosome or TBP reveal the architecture of the different functional domains of the co-activator. An octamer of histone fold domains is found at the core of SAGA. This octamer, which deviates considerably from the symmetrical analogue forming the nucleosome, establishes a peripheral site for TBP binding where steric hindrance represses interaction with spurious DNA. The structures point to a mechanism for TBP delivery and release from SAGA that requires TFIIA and whose efficiency correlates with the affinity of DNA to TBP. These results provide a structural basis for understanding specific TBP delivery onto gene promoters and the role played by SAGA in regulating gene expression. The properties of the TBP delivery machine harboured by SAGA are compared with the TBP loading device present in the TFIID complex and show multiple similitudes.","PeriodicalId":12261,"journal":{"name":"FEBS Journal","volume":"288 10","pages":"3135-3147"},"PeriodicalIF":5.4,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/febs.15563","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38493958","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: 8

Regulation of bacterial ATP synthase activity: A gear-shifting or a pawl-ratchet mechanism? 细菌ATP合酶活性的调节:是齿轮变速还是棘爪棘轮机制?

IF 5.4 2区生物学

FEBS Journal Pub Date : 2021-05-01 Epub Date: 2020-12-30 DOI: 10.1111/febs.15671

Héctor Miranda-Astudillo, Mariel Zarco-Zavala, José J García-Trejo, Diego González-Halphen

引用次数: 7

Protonation status and control mechanism of flavin-oxygen intermediates in the reaction of bacterial luciferase. 细菌荧光素酶反应中黄素-氧中间体的质子化状态及调控机制。

IF 5.4 2区生物学

FEBS Journal Pub Date : 2021-05-01 Epub Date: 2020-12-16 DOI: 10.1111/febs.15653

Ruchanok Tinikul, Narin Lawan, Nattanon Akeratchatapan, Panu Pimviriyakul, Wachirawit Chinantuya, Chutintorn Suadee, Jeerus Sucharitakul, Pirom Chenprakhon, David P Ballou, Barrie Entsch, Pimchai Chaiyen

{"title":"Protonation status and control mechanism of flavin-oxygen intermediates in the reaction of bacterial luciferase.","authors":"Ruchanok Tinikul, Narin Lawan, Nattanon Akeratchatapan, Panu Pimviriyakul, Wachirawit Chinantuya, Chutintorn Suadee, Jeerus Sucharitakul, Pirom Chenprakhon, David P Ballou, Barrie Entsch, Pimchai Chaiyen","doi":"10.1111/febs.15653","DOIUrl":"https://doi.org/10.1111/febs.15653","url":null,"abstract":"Bacterial luciferase catalyzes a bioluminescent reaction by oxidizing long-chain aldehydes to acids using reduced FMN and oxygen as co-substrates. Although a flavin C4a-peroxide anion is postulated to be the intermediate reacting with aldehyde prior to light liberation, no clear identification of the protonation status of this intermediate has been reported. Here, transient kinetics, pH variation, and site-directed mutagenesis were employed to probe the protonation state of the flavin C4a-hydroperoxide in bacterial luciferase. The first observed intermediate, with a λmax of 385 nm, transformed to an intermediate with a λmax of 375 nm. Spectra of the first observed intermediate were pH-dependent, with a λmax of 385 nm at pH < 8.5 and 375 at pH > 9, correlating with a pKa of 7.7-8.1. These data are consistent with the first observed flavin C4a intermediate at pH < 8.5 being the protonated flavin C4a-hydroperoxide, which loses a proton to become an active flavin C4a-peroxide. Stopped-flow studies of His44Ala, His44Asp, and His44Asn variants showed only a single intermediate with a λmax of 385 nm at all pH values, and none of these variants generate light. These data indicate that His44 variants only form a flavin C4a-hydroperoxide, but not an active flavin C4a-peroxide, indicating an essential role for His44 in deprotonating the flavin C4a-hydroperoxide and initiating chemical catalysis. We also investigated the function of the adjacent His45; stopped-flow data and molecular dynamics simulations identify the role of this residue in binding reduced FMN.","PeriodicalId":12261,"journal":{"name":"FEBS Journal","volume":"288 10","pages":"3246-3260"},"PeriodicalIF":5.4,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/febs.15653","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38348209","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: 9

Review for "Immune sensing of mouse polyomavirus DNA by p204 and cGAS DNA sensors" “p204和cGAS DNA传感器对小鼠多瘤病毒DNA的免疫传感”综述

IF 5.4 2区生物学

FEBS Journal Pub Date : 2021-04-22 DOI: 10.1111/febs.15962/v1/review1

Andrew MacDonald

引用次数: 0

Allosteric communication regulates ligand-specific GPCR activity. 异构通讯调节配体特异性 GPCR 活性。

IF 5.5 2区生物学

FEBS Journal Pub Date : 2021-04-01 Epub Date: 2021-04-05 DOI: 10.1111/febs.15826

Ning Ma, Anita K Nivedha, Nagarajan Vaidehi

{"title":"Allosteric communication regulates ligand-specific GPCR activity.","authors":"Ning Ma, Anita K Nivedha, Nagarajan Vaidehi","doi":"10.1111/febs.15826","DOIUrl":"10.1111/febs.15826","url":null,"abstract":"G protein-coupled receptors (GPCRs) are membrane-bound proteins that are ubiquitously expressed in many cell types and take part in mediating multiple signaling pathways. GPCRs are dynamic proteins and exist in an equilibrium between an ensemble of conformational states such as inactive and fully active states. This dynamic nature of GPCRs is one of the factors that confers their basal activity even in the absence of any ligand-mediated activation. Ligands selectively bind and stabilize a subset of the conformations from the ensemble leading to a shift in the equilibrium toward the inactive or the active state depending on the nature of the ligand. This ligand-selective effect is achieved through allosteric communication between the ligand binding site and G protein or β-arrestin coupling site. Similarly, the G protein coupling to the receptor exerts the allosteric effect on the ligand binding region leading to increased binding affinity for agonists and decreased affinity for antagonists or inverse agonists. In this review, we enumerate the current state of our understanding of the mechanism of allosteric communication in GPCRs with a specific focus on the critical role of computational methods in delineating the residues involved in allosteric communication. Analyzing allosteric communication mechanism using molecular dynamics simulations has revealed (a) a structurally conserved mechanism of allosteric communication that regulates the G protein coupling, (b) a rational structure-based approach to designing selective ligands, and (c) an approach to designing allosteric GPCR mutants that are either ligand and G protein or β-arrestin selective.","PeriodicalId":12261,"journal":{"name":"FEBS Journal","volume":"288 8","pages":"2502-2512"},"PeriodicalIF":5.5,"publicationDate":"2021-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9805801/pdf/nihms-1858383.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10864753","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