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检索条件"任意字段=中国生物化学与分子生物学会第十一次会员代表大会暨2014年全国学术会议"

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Screening of chemoeffectors for Chemoreceptor Tsr to disclose the possible molecular mechanism of repellents

Screening of chemoeffectors for Chemoreceptor Tsr to disclos...

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中国生物化学与分子生物学会第十一次会员代表大会暨2014年全国学术会议

作者：陈曦马晓旻来鲁华北京大学前沿交叉学科研究院定量生物学中心北京大学化学与分子工程学院

Chemotaxis is a phenomenon that motile bacteria move directionally alone chemicalgradients in the *** ability depends on the chemoreceptors which can detectminute concentration changes in the chemical environment,and generate a highlyamplified signal that modulates the cell’s flagella motor *** aretransmembrane proteins including periplasm domain,transmembrane domain and *** exist as trimer of dimers in *** are five types of chemoreceptorsin ***:Tar for aspartate,Tsr for serine,Tap for peptides,Trg for ribose and galactoseand Aer for *** cytoplasm domains of these receptors are highly conserved,andthe ligand selectivity depends on the periplasm *** Bi et *** discoveredsix novel attractants and two antagonists for the Escherichia coli chemoreceptorTar and revealed the molecular mechanisms for attractants binding and ***,no repellent molecules have been discovered,and the molecular mechanism ofrepellent remains *** research focus on another chemoreceptor,*** want todiscovery the chemoeffectors of Tsr and explore the molecular mechanism of repellentbinding and ***,Autodock was used to virtually screen compounds that bind toTsr ligand binding *** the potential chemoeffectors virtually screened out,fourattractants and four repellents were discovered in microfluidic *** bindingaffinity of these molecule with Tsr periplasm domain was measured by Isothermal titrationcalorimetry(ITC)and Microscale Thermophoresis(MST).Then we will verify the responseof the chemotaxis signal pathway to these chemoeffectors and explore the molecularmechanisms of the chemoeffectors,especially repellents,binding and signaling.

关键词： chemoreceptor Tsr molecular mechanism

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Denaturant effect on free energy of protein unfolding process

Denaturant effect on free energy of protein unfolding proces...

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中国生物化学与分子生物学会第十一次会员代表大会暨2014年全国学术会议

作者：李茂东刘志荣北京大学定量生物学中心

Protein denaturation refers to its specific spatial conformation change according to thecertain physical or chemical *** of the research in the past is carried out on theensemble *** was found that the free energy change was linear with the concentrationof *** ensemble describes average properties of the system,but the probabilisticinformation of different states in the system is *** single molecule methodsmake it possible to work on these *** are two main models for protein denaturation,one is Transfer model,another is Binding *** analyzed the free energychange in the process of protein denaturation and the universality of the two *** the transfer model,it was found that the protein residue interactions energy differenceεdepends linearly on the denaturant concentration,and that the free energy of denatured-state collapse has a linear dependence on denaturant *** we foundthat the collapsed state was far away from the equilibrium state,which could only providea reference state for native state but not an intermediate *** that the coil-to-globuletransition of the denatured state didn’t appear in protein folding,suggesting that conformationalentropy of the denatured state was not so important as *** addition,we found out the neglected collapsed-to-native free energy could describe the specificinteraction in folding,which was independent of the denaturant concentration but linearlydependent on residue *** the binding model,it was assumed that there are identical independent binding siteswith an effective association constant,which could not satisfy the linearity between thefree energy change and the denaturant *** achieve a linear relationship,itwas found that an abnormal dependence of activity on the denaturant concentration hasto been *** conclusion,Transfer model is a good mechanism for protein denaturation,while Bindingmodel remains to be optimized.

关键词： Protein denaturation transfer model binding model

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Decreased expression of nicotinic acetylcholine receptor in the hippocampus of vascular dementia rats and in blood leukocytes from Chinese patients with vascular dementia

Decreased expression of nicotinic acetylcholine receptor in ...

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中国生物化学与分子生物学会第十一次会员代表大会暨2014年全国学术会议

作者：肖雁 Hang Jing Mao Tan Yan-jun Dong Xiao-lan Qi Zhi-zhong Guan 贵阳医学院分子生物学重点实验室贵阳医学院研究生院贵阳医学院分子生物学重点实验室病理教研室

In order to investigate the cholinergic deficit in Vascular dementia(VaD),fifty-nine Chinesepatients with VaD and thirty-onecases as the age-matched controls in China were selectedand to establish the similar animal model of vascular dementia(VaD)Pulsinelli’s fourvesselocclusion,to nurture the VaD rats,and Morris water maze experiment is used to testthe cognition abilityof the *** mRNA levels ofα4 andβ2 nicotinic acetylcholine receptor(nAChR)subunits in blood leukocytes of patientandβ2,α4,α7nAChR subunits inhippocampus of rats were analyzed by Real-Time PCR,the protein level ofβ2,α4,α7nAChRsubunit in the hippocampus of rats were analyzed by western *** results showedthat mRNA levels ofα4 nAChRsubunit in blood leukocytes was significantly lower in VaDgroup than that in controls,mRNA levels ofβ2,α7 nAChR subuniin the hippocampus wassignificantly lower in VaD group than that in controls in rats,respectively,the mRNA levelof thesubunit ofα4 increased;The expression of theβ2,α4,α7 nAChR subunit protein wassignificantly *** resultindicated that the decreases in the mRNA levels of nAChRα4 subunit from the peripheral blood of the patients with VaDmight serve as supplementaryindicators for the clinical diagnosis of *** decrease of nAChR of hippocampusneuronscan possibly be the foundation of the injury of the cognition function of theVaD rats.

关键词： learning and memory Nicotinic acetylcholine receptor Vascular dementia A nimals model

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The functional and structure study of phosphatidylinositol 4-kinase IIalpha

The functional and structure study of phosphatidylinositol 4...

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中国生物化学与分子生物学会第十一次会员代表大会暨2014年全国学术会议

作者：陈畅中国科学院生物物理研究所

Phosphatidylinositol(PI)4-kinase IIα(PI4KIIα)is the dominant PI4K in mammalian cells andplays important roles in membrane trafficking and signaling *** report forthe first time that PI4KIIαcan promote the growth of multimalignant tumors[1].Our furtherstudy showed that PI4KIIαhas pivotal role in the regulation of EGFR protein levels andcombinatorial inhibition of PI4KIIαand EGFR showed strong anti-tumor effect[2].To knowthe kinase activity regulation mechanism,we then solved the crystal structure of humanPI4KIIαcatalytic domain in its ADP-bound form at *** novel insertionsthat are not present in other PIKs were found in PI4KIIα.The palmitoylation insertion andRK-rich insertion are critical for the regulation of PI4KIIα’s membrane binding and kinaseactivity.A distinct nucleotidebinding pocket of PI4KIIαwas found that differs notablyfrom that of PI3Ks,which well explained the insensitivity of PI4KIIαto PI3Ks’*** dynamics stimulation,biochemical and mutagenesis studies reveal that any perturbationof the interaction between PI4KIIαand membrane will affect either the nucleotidebinding or PI binding and then modulate the kinase activity of PI4KIIα[3].Screeningfor a subtype specific inhibitor for PI4KIIαis undergoing.

关键词： phosphatidylinositol 4-kinase IIalpha functional structure

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The RanGTP-modulation of Mog1 is required for faithful mitotic chromosome segregation

The RanGTP-modulation of Mog1 is required for faithful mitot...

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中国生物化学与分子生物学会第十一次会员代表大会暨2014年全国学术会议

作者：刘恒中国科技大学

The role of the small GTPase Ran in spindle assembly has been recently uncovered to ensurethe correct chromosome segregation and thus genetic stability in mammalian *** Mog1,as the Ran nucleotide release factor,can downregulate RanGTP in vitro,but the underlying molecular mechanism for Mog1 modulating the function of Ran *** Ran crystal structure has been solved,the structural characterizationof the Mog1/Ran complex remains a challenge due to the dynamic nature of their *** is particularly suited to elucidate the structure and dynamics of proteincomplexes even there are conformational ***,therefore,solved the solutionstructure of human Mog1(hMog1)at *** overcome the NMR size limitation,we recruitedthe methyl-TROSY based NMR approaches,e.g.,intra-molecular methyl NOEs andsite-directed mutations for the complex methyl chemical shift assignment,and intermolecularmethyl NOEs,Paramagnetic relaxation enhancement(PRE),Residual dipolarcouplings(RDCs)to generate the structural model of hMog1/Ran *** structuralmodel indicated interfacial residues crucial for the GTP/GDP releasing from Ran catalyzedby Mog1,such loss-of-function mutations were thereafter validated by in vitro binding andenzymatic ***,the depletion and overexpression of Mog1 induced defectsin mitotic chromosomes alignment in living cells,while the loss-of-function mutants *** the RanGTP gradient was also disrupted due to the aberrant hMog1 level usingRango2 ***,we conclude that hMog1 plays an important role in mitotic chromosomesegregation by regulating the RanGTP level.

关键词： RanGTP mitosis

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SAHA Treatment Reveals the Link between Histone Lysine Acetylation and Proteome in Nonsmall Cell Lung Cancer A549 Cells

SAHA Treatment Reveals the Link between Histone Lysine Acety...

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中国生物化学与分子生物学会第十一次会员代表大会暨2014年全国学术会议

作者： Zhongyi Cheng PTM Biolabs Inc

Suberoylanilide hydroxamic acid(SAHA) is a well-known pan HDAC inhibitor, and its clinicalapplication(Vorinostat) has been demonstrated to treat nonsmall cell lung cancer(NSCLS). Nevertheless, the impact of SAHA treatment on histone lysineacetylation and proteome in NSCLS cells still need further elucidate. In NSCLS A549 cells, by using stableisotope labeling for cell culture(SILAC)-based quantitative proteomics, biochemistry assay,and bioinformatic analysis, here we for the first time comprehensively identified and quantifiedhistone lysine acetylation in A549 cells toward SAHA treatment. Despite the fact that SAHA treatment significantly increased histone lysine acetylation in specific sites, unexpectedly,some important "histone markers" showed markedly decreased acetylation *** quantitative proteome studies showed that among totally quantifiable 2818 non redundant proteins, 1355 proteins were with increased level and 1463 with decreased level in response to SAHA treatment. Bio informatic analysis further revealed that those quantifiable proteins were mainly involved in multiple biological functions and metabolic and enzyme-regulated pathways as well as protein complexes. By establishing the link between histone modification and whole proteome in response to SAHA treatment in NSCLS cells,this study therefore may deepen our understanding of HDAC inhibitor-mediated cancer therapeutics.

关键词： Histone Lysine Acetylation Non small Cell Lung Cancer Suberoylanilide hydroxamic acid HDAC inhibitor Drug targets Biomarker

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Intramolecular Regulation of the WW Domain of HYPB/SETD2 for Its Sequestration by the Huntingtin Aggregates

Intramolecular Regulation of the WW Domain of HYPB/SETD2 for...

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中国生物化学与分子生物学会第十一次会员代表大会暨2014年全国学术会议

作者： Yong-Guang Gao Hui Yang Jian Zhao Ya-Jun Jiang Hong-Yu Hu State Key Laboratory of Molecular Biology Institute of Biochemistry and Cell Biology SIBS CAS

Huntington's disease(HD)is a progressive neurodegenerative disorder caused by thepolyglutamine(polyQ)expansion in huntingtin(Htt)protein,a ubiquitously expressed proteinof yet unknown *** its public health importance,it is striking that thepathogenesis of HD is not well ***,how Htt aggregates affect thephysiological processes of its effector proteins are largely unknown and this is one of thecentral questions about the pathology of *** yeast two-hybrid protein B(HYPB/SETD2)is a histone methyltransferase directly interacting with Htt and is involved in HD *** this work,we found that a majority of the WW domain in HYPB was intramolecularlly inhibitedby a polyproline(polyP)stretch *** solved the solution structure of the inhibitedWW domain and found that the polyP stretch extends from the back binding tothe WW core domain in a typical binding *** also found that this polyP stretchsignificantlyregulates the interaction of the WW domain of HYPB with the proline-rich region(PRR)of ***,sequestration of the WW domain of HYPB by the Htt aggregateswas orchestrated by the PolyP stretch in cell *** is the first evidence indicatingthat the interactions of Htt with its effector proteins are regulated,which provides anopportunity for therapeutic *** study gains structural and mechanistic insightsinto the intramolecular regulation of the WW domain in HYPB for interacting withHtt and the sequestration of HYPB by the Htt aggregates,which will contribute to our understandingof the pathology of HD.

关键词： Huntingtin HYPB/SETD2 Intramolecular interaction Aggregate Sequestration Proline-rich region WW domain

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MIF intersubunit disulfide mutant antagonist supports activation of CD74 by endogenous MIF trimer at physiologic concentrations

MIF intersubunit disulfide mutant antagonist supports activa...

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中国生物化学与分子生物学会第十一次会员代表大会暨2014年全国学术会议

作者：范成鹏 Elias Lolis 武汉大学 Yale University

Macrophage migration inhibitory factor(MIF)is a proinflammatory *** addition toits known receptor-mediated biological activities,MIF possesses a catalytic site of unknownfunction between subunits of a *** subunit contributes threeβ-strands toadjacent subunits to form a core seven-strandedβ-sheet for each ***,dimers,or trimers have been reported,but the active form that binds and activatesthe MIF receptor(CD74)is still a matter of debate.A cysteine mutant(N110C)thatcovalently locks MIF into a trimer by forming a disulfide with Cys-80of an adjacent subunit is used to study this *** catalytic activity and receptorbinding to CD74 are retained by N110C(locked trimer),but there is no cellular ***-type MIF-induced cellular signaling,in vivo lung neutrophil accumulation,and alveolarpermeability are inhibited with a fivefold excess of *** size-exclusion chromatography with light scattering reveal that N110C can form ahigher-order oligomer in equilibrium with a single locked *** X-ray structure confirmsa local conformational change that disrupts the subunit interface and results in globalchanges responsible for the oligomeric *** structure also confirms these changesare consistent for the partial catalytic and receptor binding *** absence of anypotential monomer and the retention of partial catalytic and receptor binding activitiesdespite changes in conformation(and dynamics)in the mutant support an endogenousMIF trimer that binds and activatesCD74 at nanomolar *** conclusion has implications for therapeutic development.

关键词： MIF strcuture mechanism

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IQGAP1 is involved in cell migration by interacting with γ-cateninin hepatocellular carcinoma

IQGAP1 is involved in cell migration by interacting with γ-...

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中国生物化学与分子生物学会第十一次会员代表大会暨2014年全国学术会议

作者： Xuewen Jin Yuling Liu Weiliang Lu Bing Chen Jingjing Liu Peng Zhang Shufang Liang State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy West China Hospital Sichuan University West China Hospital Sichuan University

The IQ-domain GTPase-activating protein 1(IQGAP1) is a multifunctional scaffold protein,which interacts with diverse proteins to regulate cell adhesion and cell migration. And theabnormal expression of IQGAP1 widely exists in many cancers, the molecular mechanismof IQGAPs in tumorigenesis remains to clarify. We have found that IQGAP1 is overexpressedin hepatocellular carcinoma(HCC) cell lines and HCC tumor tissues. The expressionlevels of IQGAP1 are positively associated with the metastasis ability of HCC cells. Theup-regulation of IQGAP1 improves the expression of β-catenin and the migration ability ofHepG2 cells. Meanwhile, the knockdown of IQGAP1 by siRNA results in the decrease of β-catenin expression and cell migration in vitro. Furthermore, the protein expression ofIQGAP1 and β-catenin are respectively upregulated in 54.55% and 45.45% of human HCCtumor samples(n=11) compared with the para-cancerous liver tissues. Generally the higher expressions and interactions of IQGAP1 and β-catenin contribute to HCC tumori genesisby promoting cell growth and cell migration.

关键词： IQGAP1 β-catenin Hepatocellular carcinoma Cell migration

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Oxidative stress is an important factor triggering the aggregation of cataract-causing γ-crystallin mutants

Oxidative stress is an important factor triggering the aggre...

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中国生物化学与分子生物学会第十一次会员代表大会暨2014年全国学术会议

作者：赵维杰闫永彬 State Key Laboratory of Biomembrane and Membrane Biotechnology School of Life Sciences Tsinghua University

Crystallins are the major structural proteins in mammalian lens and their stability is essentialfor the lens to maintain transparency throughout one individual’s *** normallens,the crystallins are protected from oxidization by the high concentration of glutathione(GSH)within the *** in the case of aging cataract lens,the GSH concentrationis decreased and proteins including crystallins undergo oxidization and lose the abilityto maintain stable and *** that many cataract-causing mutations are substituted by oxidable residues,here we asked whether oxidization plays a role in the onset of congenital *** was addressed by studying the behaviors ofγC andγD crystallin and variouscataract-causing mutatants under oxidative *** results showed that under oxidativestress,theγD mutants R14C and G60C formed dimer via intermolecular disulfidebond,while the WTγD and the mutant R58H didn’*** proteins showed decreasedthermo stability and the impairment was ever serious.R58H showed no significant differencewith WT protein in thermo stability in absence of oxidization,while became lessstable than WT after *** further found that theγC proteins were more sensitiveto oxidization thenγD *** the WT and mutated proteins were crosslinkedafter *** the cataract-causing mutants exhibited a much lower thermo stabilitythan the WT *** results suggested that the cataract-causing mutations significantlyincreased the sensitivity to oxidative *** might be an importantfactors involved in the progression of congenital cataract caused by inherited mutations.

关键词： Crystallin oxidative stress cataract

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