简介：Inthefaceoftheworldwidethreatofsevereacuterespiratorysyndrome(SARS)tohumanlife,someofthemosturgentchallengesaretodevelopfastandaccurateanalyticalmethodsforearlydiagnosisofthisdiseaseaswellastocreateasafeanti-viralvaccineforprevention.Totheseends,weinvestigatedtheantigenicityofthespikeprotein(Sprotein),amajorstructuralproteinintheSARS-coronavirus(SARS-CoV).BaseduponthetheoreticalanalysisforhydrophobicityoftheSprotein,18peptidesweresynthesized.UsingEnzyme-LinkedImmunosorbentAssay(ELISA),thesepeptideswerescreenedintheserafromSARSpatients.Accordingtotheseresults,twofragmentsoftheSgenewereamplifiedbyPCRandclonedintopET-32a.BothSfragmentswereexpressedintheBL-21strainandfurtherpurifiedwithanaffinitychromatography.TheserecombinantSfragmentswereconfirmedtohavepositivecross-reactionswithSARSsera,eitherbyWesternblotorbyELISA.OurresultsdemonstratedthatthepotentialepitoperegionswerelocatedatCodons469-882intheSprotein,andoneepitopesitewaslocatedatCodons599-620.IdentificationofantigenicregionsintheSARS-CoVSproteinmaybeimportantforthefunctionalstudiesofthisvirusorthedevelopmentofclinicaldiagnosis.

简介：AbstractSwine acute diarrhea syndrome coronavirus (SADS-CoV) is a recently discovered coronavirus that causes severe and acute diarrhea and rapid weight loss in piglets. SADS-CoV was reported to be capable of infecting cell lines derived from diverse species, including bats, mice, hamsters, rats, chickens, pigs, nonhuman primates, and humans, implying its high risk of cross-species infection. However, its receptor is still unknown. In this study, the receptor-binding domain of the SADS-CoV spike (S) protein was purified and then subjected to affinity purification (AP)-coupled mass spectrometry (MS)-based proteomic analysis to identify the interactors of the SADS-CoV S protein. Forty-three host proteins were identified, and a Gene Ontology analysis indicated that these interactors can be grouped into categories such as "cell-cell adhesion" , "translation" "viral transcription" , suggesting that these processes may participate in the SADS-CoV life cycles. RNA interference-based screening of these interactors indicated that PPIB and vimentin can affect SADS-CoV replication. Our study provides an overarching view into the host interactome of the SADS-CoV S protein and highlights potential targets for the development of therapeutics against SADS-CoV.

简介：AbstractBackground:Coronavirus can cross the species barrier and infect humans with a severe respiratory syndrome. SARS-CoV-2 with potential origin of bat is still circulating in China. In this study, a prediction model is proposed to evaluate the infection risk of non-human-origin coronavirus for early warning.Methods:The spike protein sequences of 2666 coronaviruses were collected from 2019 Novel Coronavirus Resource (2019nCoVR) Database of China National Genomics Data Center on Jan 29, 2020. A total of 507 human-origin viruses were regarded as positive samples, whereas 2159 non-human-origin viruses were regarded as negative. To capture the key information of the spike protein, three feature encoding algorithms (amino acid composition, AAC; parallel correlation-based pseudo-amino-acid composition, PC-PseAAC and G-gap dipeptide composition, GGAP) were used to train 41 random forest models. The optimal feature with the best performance was identified by the multidimensional scaling method, which was used to explore the pattern of human coronavirus.Results:The 10-fold cross-validation results showed that well performance was achieved with the use of the GGAP (g = 3) feature. The predictive model achieved the maximum ACC of 98.18% coupled with the Matthews correlation coefficient (MCC) of 0.9638. Seven clusters for human coronaviruses (229E, NL63, OC43, HKU1, MERS-CoV, SARS-CoV, and SARS-CoV-2) were found. The cluster for SARS-CoV-2 was very close to that for SARS-CoV, which suggests that both of viruses have the same human receptor (angiotensin converting enzyme II). The big gap in the distance curve suggests that the origin of SARS-CoV-2 is not clear and further surveillance in the field should be made continuously. The smooth distance curve for SARS-CoV suggests that its close relatives still exist in nature and public health is challenged as usual.Conclusions:The optimal feature (GGAP, g = 3) performed well in terms of predicting infection risk and could be used to explore the evolutionary dynamic in a simple, fast and large-scale manner. The study may be beneficial for the surveillance of the genome mutation of coronavirus in the field.

简介：蛋白质领域被保存，在相互作用起一个重要作用在之中的机能上地独立的结构联系了蛋白质。域域相互作用最近被用来预言蛋白质蛋白质相互作用(PPI)。一般来说，一双领域的相互作用概率用训练得分功能被获得。令人满意阀值，当“交往”，带那些领域的蛋白质对被考虑。在这研究，蛋白质的签名内容被利用在Saccharomycescerevisiae，Caenorhabditiselegin，和人预言PPI对现代人。蛋白质签名模式的类似被获得，PPI预言基于二进制类似得分函数被拉。结果证明由建议途径的预言的真积极的率用最大的可能性评价方法比那高是约32%，导致在与一个测试集合相比操作的接收装置下面的区域的22%增加什么时候特征(巨鸟)曲线。当包含一个或二签名的蛋白质被移开时，预言的PPI对的敏感显著地增加了。预言的PPI对是平均，11更多半预定在0.95的信心水平比随机的选择交往，并且平均，4比那些由也预言更好预定种系发生的介绍或基因表达介绍。

简介：

简介：Thecorona-likespikesorpeplomersonthesurfaceofthevirionunderelectronicmicroscopearethemoststrikingfeaturesofcoronaviruses.TheS(spike)proteinisthelargeststructuralprotein,with1,255aminoacids,intheviralgenome.Itsstructurecanbedividedintothreeregions:alongN-terminalregionintheexte-rior,acharacteristictransmembrane(TM)region,andashortC-terminusintheinteriorofavirion.WedetectedfifteensubstitutionsofnucleotidesbycomparisonswiththeseventeenpublishedSARS-CoVgenomesequences,eight(53.3%)ofwhicharenon-synonymousmutationsleadingtoaminoacidalternationswithpredictedphysiochemicalchanges.ThepossibleantigenicdeterminantsoftheSproteinarepredicted,andtheresultisconfirmedbyELISA(enzyme-linkedimmunosorbentassay)withsynthesizedpeptides.AnotherprofoundfindingisthatthreedisulfidebondsaredefinedattheC-terminuswiththeN-terminusoftheE(envelope)pro-tein,basedonthetypicalsequenceandpositions,thusestablishingthestructuralconnectionwiththesetwoimportantstructuralproteins,ifconfirmed.Phyloge-neticanalysisrevealsseveralconservedregionsthatmightbepotentdrugtargets.

简介：

简介：AbstractBackground:The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) is pandemic. However, the origins and global transmission pattern of SARS-CoV-2 remain largely unknown. We aimed to characterize the origination and transmission of SARS-CoV-2 based on evolutionary dynamics.Methods:Using the full-length sequences of SARS-CoV-2 with intact geographic, demographic, and temporal information worldwide from the GISAID database during 26 December 2019 and 30 November 2020, we constructed the transmission tree to depict the evolutionary process by the R package "outbreaker" . The affinity of the mutated receptor-binding region of the spike protein to angiotensin-converting enzyme 2 (ACE2) was predicted using mCSM-PPI2 software. Viral infectivity and antigenicity were tested in ACE2-transfected HEK293T cells by pseudovirus transfection and neutralizing antibody test.Results:From 26 December 2019 to 8 March 2020, early stage of the COVID-19 pandemic, SARS-CoV-2 strains identified worldwide were mainly composed of three clusters: the Europe-based cluster including two USA-based subclusters; the Asia-based cluster including isolates in China, Japan, the USA, Singapore, Australia, Malaysia, and Italy; and the USA-based cluster. The SARS-CoV-2 strains identified in the USA formed four independent clades while those identified in China formed one clade. After 8 March 2020, the clusters of SARS-CoV-2 strains tended to be independent and became "pure" in each of the major countries. Twenty-two of 60 mutations in the receptor-binding domain of the spike protein were predicted to increase the binding affinity of SARS-CoV-2 to ACE2. Of all predicted mutants, the number of E484K was the largest one with 86 585 sequences, followed by S477N with 55 442 sequences worldwide. In more than ten countries, the frequencies of the isolates with E484K and S477N increased significantly. V367F and N354D mutations increased the infectivity of SARS-CoV-2 pseudoviruses (P < 0.001). SARS-CoV-2 with V367F was more sensitive to the S1-targeting neutralizing antibody than the wild-type counterpart (P < 0.001).Conclusions:SARS-CoV-2 strains might have originated in several countries simultaneously under certain evolutionary pressure. Travel restrictions might cause location-specific SARS-CoV-2 clustering. The SARS-CoV-2 evolution appears to facilitate its transmission via altering the affinity to ACE2 or immune evasion.

简介：AbstractThe present pandemic has posed a crisis to the economy of the world and the health sector. Therefore, the race to expand research to understand some good molecular targets for vaccine and therapeutic development for SARS-CoV-2 is inevitable. The newly discovered coronavirus 2019 (COVID-19) is a positive sense, single-stranded RNA, and enveloped virus, assigned to the beta CoV genus. The virus (SARS-CoV-2) is more infectious than the previously detected coronaviruses (MERS and SARS). Findings from many studies have revealed that S protein and RdRp are good targets for drug repositioning, novel therapeutic development (antibodies and small molecule drugs), and vaccine discovery. Therapeutics such as chloroquine, convalescent plasma, monoclonal antibodies, spike binding peptides, and small molecules could alter the ability of S protein to bind to the ACE-2 receptor, and drugs such as remdesivir (targeting SARS-CoV-2 RdRp), favipir, and emetine could prevent SASR-CoV-2 RNA synthesis. The novel vaccines such as mRNA1273 (Moderna), 3LNP-mRNAs (Pfizer/BioNTech), and ChAdOx1-S (University of Oxford/Astra Zeneca) targeting S protein have proven to be effective in combating the present pandemic. Further exploration of the potential of S protein and RdRp is crucial in fighting the present pandemic.

简介：TheE(envelope)proteinisthesmalleststructuralproteininallcoronavirusesandistheonlyviralstructuralproteininwhichnovariationhasbeendetected.WeconductedgenomesequencingandphylogeneticanalysesofSARS-CoV.Basedongenomesequencing,wepredictedtheEproteinisatransmembrane(TM)pro-teincharacterizedbyaTMregionwithstronghydrophobicityandα-helixcon-formation.Weidentifiedasegment(NH2-_L-Cys-A-Y-Cys-Cys-N_-COOH)inthecarboxyl-terminalregionoftheEproteinthatappearstoformthreedisulfidebondswithanothersegmentofcorrespondingcysteinesinthecarboxyl-terminusoftheS(spike)protein.ThesebondspointtoapossiblestructuralassociationbetweentheEandSproteins.OurphylogeneticanalysesoftheEproteinsequencesinallpub-lishedcoronavirusesplaceSARS-CoVinanindependentgroupinCoronaviridaeandsuggestanon-humananimalorigin.

简介：Theadsorptionofproteinonnanoparticleswasstudiedbyusingdynamiclightscatteringtomeasurethehydrodynamicsizeofbothpureproteinandnanoparticlesadsorbedwithdifferentamountsofprotein.Thethicknessoftheadsorbedproteinlayerincreasesasproteinconcentration,butdecreasesastheinitialsizeofnanoparticles.Afterproperlyscalingthethicknesswiththeinitialdiameter,weareabletofitallexperimentaldatawithasinglemastercurve.Ourexperimentalresultssuggestthattheadsorbedproteinsformamonolayeronthenanoparticlesurfaceandtheadsorbedproteinmoleculesareattachedtotheparticlesurfaceatmanypointsthroughapossiblehydrogen-bonding.Ourresultsalsoindicatethatasproteinconcentrationincreases,theoverallshapeoftheadsorbedproteinmoleculecontinuouslychangesfromaflatlayerontheparticlesurfacetoastretchedcoilextendedintowater.Duringthechange,thehydrodynamicvolumeoftheadsorbedproteinincreaseslinearlywithproteinconcentration.

简介：管理生命的自然现象的内在的原则是在最近的年里收到到期的重要性的关键问题之一。没有规模的建筑学的特色是大多数连接节点(中心)的活力。这篇文章的主要目的是由在二个相互作用系统的拓扑的参数上考虑建筑上的模式和中心的移动的后果分析蛋白质蛋白质和果蝇melanogaster的新陈代谢的相互作用网络。分析证明两个相互作用网络跟随一个没有规模的模型，建立从改变的状况，很真实的世界网络遵循小世界模式的事实。平均路径长度出现了一双重并且三方面的增加(从9.42～20.93并且从5.29～17.75变化，分别地)分别地，由于中心的删除为蛋白质蛋白质和新陈代谢的相互作用联网。相反，节点的任意的消除没在蛋白质蛋白质和新陈代谢的相互作用网络的拓扑的参数显示出任何显著不同(平均路径长度：9.42+/-0.02和5.27+/-0.01，分别地)。为二个盒子的这越轨行为强调大多数连接节点的意义到网络的自然拓扑学。

简介：Protein-proteininteractions(PPIs)havebeenwidelystudiedtounderstandthebiologicalprocessesormolecularfunctionsassociatedwithdifferentdiseasesystemslikecancer.Whilefocusedstudiesonindividualcancershavegeneratedvaluableinformation,globalandcomparativeanalysisofdatasetsfromdifferentcancertypeshasnotbeendone.Inthiswork,wecarriedoutbioinformaticanalysisofPPIscorrespondingtodifferentiallyexpressedgenesfrommicroarraysofvarioustumortissues(belongingtobladder,colon,kidneyandthyroidcancers)andcomparedtheirassociatedbiologicalprocessesandmolecularfunctions(basedonGeneOntologyterms).Weidentifiedasetofprocessesorfunctionsthatarecommontoallthesecancers,aswellasthosethatarespecifictoonlyoneorpartialcancertypes.Similarly,proteininteractionnetworksinnucleicacidmetabolismwerecomparedtoidentifythecommon/specificclustersofproteinsacrossdifferentcancertypes.Ourresultsprovideabasisforfurtherexperimentalinvestigationstostudyproteininteractionnetworksassociatedwithcancer.Themethodologydevelopedinthisworkcanalsobeappliedtostudysimilardiseasesystems.

简介：ProteinkinaseRAFisstrategicallylocatedinthe'Ras-MAP-kinasesignaltransductionpathway',aprinciplesystemwhichtransmitssignalsfromgrowthfactorreceptorstothenucleus,resultingincellproliferation.GrowthfactorresponsesaremediatedinpartbyactivationofRas,whichinturnactivatesRAFtophosphorylateMEK,itsdownstreamsubstrate.MEKactivatesMAPkinasetoinfluencenuclearevents.itisclear.however,thatanetworkofsignalsotherthanthosecarredbyRasplaysaroleinRAFregulation.Theseorthogonalinfluencesaremediatedbu:serine/threoninekinases,tyrosinekinases,andprotein-proteininteractions.AsafurthercomplicationtotheRAFnetwork,threeisoformsofRAFhavebeenestablishedwhichhavedivergentN-terminalregulatorydomains,Whereasthesedivergentregulatorydomainsimplicateisoform-specificfunctions,noclearevidenceorhypothesisfordistinctfunctionsforindividualisoformshasbeenpresented.Recently,'isoform-specificproteininteractions'havebeenidentifiedamongnumerousproteinsinteractingwithRAF,ThesestudiesmayservetodelineateindependentfunctionsforRAFisoforms.

简介：AstatisticalthermodynamictheoryoflinearproteinsolutionswasproposedwiththeaidofalatticemodelandappliedtotypeⅠantifreezeprotein(AFPI)solutions.ThenumericalresultsforseveralAFPIsolutionsshowthattheGibbsfunctionofthesolutionhasaminimumatacertainproteinconcentration,buttheproteinchemicalpotentialincreaseswithincreasingtheconcentration.TheinfluencesoftemperatureandproteinchainlengthontheAFPIchemicalpotentialwerealsodiscussed.Theevaluationforthecolligativedepressionofthefreezingpointconfirmsthattheantifreezeactionshouldberecognizedasnon-colligative.Thetheoreticaldeductionfortheconcentrationdependenceofthethermalhysteresisactivitycoincidesqualitativelywiththepreviousexperimentalandtheoreticalresults.

简介：Transmissiblespongiformencephalopathyorpriondiseaseistriggeredbytheconversionfromcellularprionproteintopathogenicprionprotein.Growingevidencehasconcentratedonprionproteinconfigurationchangesandtheircorrelationwithpriondiseasetransmissibilityandpathogenicity.Invivoandinvitrostudieshaveshownthatseveralcytosolicformsofprionproteinwithspecifictopologicalstructurecandestroyintracellularstabilityandcontributetoprionproteinpathogenicity.Inthisstudy,thelatestmolecularchaperonesystemassociatedwithendoplasmicreticulum-associatedproteindegradation,theendoplasmicreticulumresidentproteinquality-controlsystemandtheubiquitinationproteasomesystem,isoutlined.Themolecularchaperonesystemdirectlycorrelateswiththeprionproteindegradationpathway.Understandingthemolecularmechanismswillhelpprovideafascinatingavenueforfurtherinvestigationsonpriondiseasetreatmentandprionprotein-inducedneurodegenerativediseases.

简介：AbstractCardiovascular disease (CVD) remains the leading cause of death worldwide. Therefore, exploring the mechanism of CVDs and critical regulatory factors is of great significance for promoting heart repair, reversing cardiac remodeling, and reducing adverse cardiovascular events. Recently, significant progress has been made in understanding the function of protein kinases and their interactions with other regulatory proteins in myocardial biology. Protein kinases are positioned as critical regulators at the intersection of multiple signals and coordinate nearly every aspect of myocardial responses, regulating contractility, metabolism, transcription, and cellular death. Equally, reconstructing the disrupted protein kinases regulatory network will help reverse pathological progress and stimulate cardiac repair. This review summarizes recent researches concerning the function of protein kinases in CVDs, discusses their promising clinical applications, and explores potential targets for future treatments.

简介：

简介：植物蛋白质蛋白质相互作用网络没被大规模实验识别了。以便更好在米饭理解蛋白质相互作用，预言的米饭Interactome网络(PRIN；http://bis.zju.edu.cn/prin/)介绍76,585个预言的相互作用包含5,049米饭蛋白质。在印射米饭的genomic特征以后(去注解，subcellular本地化预言，和基因表示)，我们发现一个注解得好、生物学上重要的网络是足够富有的在高顺序的生物系统以内捕获许多重要功能的连接，例如小径和生物进程。而且，我们作为例子拿了疯盒子的包含域的蛋白质和生理节奏的节奏发信号小径证明功能的蛋白质建筑群和生物小径能有效地在我们的预言的网络被扩展。在PRIN的扩展分子的网络更加改进了这些分析的能力集成存在知识并且提供新奇卓见进基因和基因网络的功能和协作。

简介：蜕皮激素受体(EcR)和ultraspiracle(USP)形成heterodimers调停ecdysteroid在molting和变形期间发信号。各种各样的EcR/USPheterodimers被报导了。然而，联合什么样的EcR/USP被鳞翅类的昆虫在幼虫蛹的变形期间采用并且EcR/USPheterodimer是否在不同纸巾之中变化，是不清楚的。探讨这些问题，每EcR和USP的二isoforms从普通糖蛾被克隆，他们的送信人RNA表示模式被即时量的聚合酶链反应响应神经质的正式就职在幼虫蛹的变形期间并且在midgut在不同纸巾检验。而且，他们的subcellular本地化和蛋白质蛋白质相互作用被短暂表示并且分别地的远西方的弄污探索。所有四基因在prepuae或蛹是显著地起来调整的。EcRB1和USP1的表示侧面与在外皮，胖身体和midgut的对方将近相同，并且一种类似的状况也适用于EcRA和USP2。三基因除了USP2，和USP1回答了正式就职到20-hydroxyecdysone(20E)能由20E和少年荷尔蒙起来调整。在原子核和原子本地化主要局部性的四蛋白质被20E支持。在每EcR和USP之间的蛋白质蛋白质相互作用在vitro被发现。这些结果建议EcR/USPheterodimer(EcRA/USP2和EcRB1/USP1)的二种类型可以在普通糖蛾同时存在，并且后者应该在幼虫蛹的变形期间起更重要的作用。另外，EcR/USPheterodimer的类型不在在变形期间经历histolysis和新生的纸巾变化。