受翻译调节的肿瘤蛋白的结构与功能

受翻译调节的肿瘤蛋白（translationally controlled tumor protein, TCTP）是一种普遍存在并且大量表达的蛋白,在进化上高度保守,与其它任何蛋白家族均未显示出明显的序列同源性.该家族的蛋白基本上都具有TCTP1和TCTP2两个特征结构区.TCTP与Mss4/Dss4(mammalian suppressor of Sec4)蛋白家族结构相似,二者构成结构超家族.TCTP的合成受到钙、真核翻译起始因子eIF4E(eukaryotic translation initiation factor 4E)和双链RNA依赖的蛋白激酶(dsRNA dependent protein kinase,PKR)的调节.具有与钙结合,与微管蛋白结合,抗细胞凋亡,抑制翻译,促进组胺释放等生物学活性.另外,它还可作为肿瘤逆转的靶标.系统发育分析提示,在真核细胞进化中, TCTP的直向同源基因起源于1.0×109年前.本文对TCTP的分子特点, 生物学功能及其研究现状进行了综述.     

Smads蛋白结构与功能的研究进展

TGF－β家族成员与细胞膜上受体结合后,通过Smads蛋白,调节细胞核内特异的基因表达。从结构和功能上看,Smads蛋白可分为3类。受体调节－Smads(R-Smads)作为具有Ser/Thr激酶活性的TGF-β受体－I的底物,激活后通过MH2结构域,与共同介导的Smads(Co-Smads）相互作用形成异聚体,直接结合在目的基因启动子上,影响基因转录。而转录抑制Smads(I-Smads)能够拮抗R－Smads的生物活性。在细胞内,Smads蛋白通过与不同的转录蛋白或转录共调节因子相互作用,在不同类型的细胞内介导特异的基因表达。改变Smads蛋白的正常结构和功能上起人体发生各种病变。     

锌指蛋白结构及功能研究进展

锌指蛋白是一类具有手指状结构域的转录因子,对基因调控起重要的作用。根据其保守结构域的不同,可将锌指蛋白主要分为C2H2型、C4型和C6型。锌指通过与靶分子DNA、RNA、DNA-RNA的序列特异性结合,以及与自身或其他锌指蛋白的结合,在转录和翻译水平上调控基因的表达。我们简要综述了近年来锌指蛋白结构、分类及其与核酸及蛋白质相互作用等方面的研究进展。     

人类神经Tau蛋白结构与功能研究进展

Ｔａｕ属微管结合蛋白,对神经细胞的生长发育,物质运输及信息传导起着重要作用。该分子不具有明显的二级结构,其生物学功能的调节功能主要是通过磷酸化和去磷酸化来实现。目前的研究表明,早老性痴呆等疾病与Ｔａｕ分子高级结构的异常改变和功能丧失有关。     

S100蛋白功能和结构研究进展

S100蛋白作为Ca2+调节蛋白广泛存在于各种脊椎动物中.它们参与调控蛋白磷酸化、酶活性、细胞增殖分化、细胞骨架组成的动力学、膜结构组成、维持细胞间Ca2+浓度的恒定、参与炎症反应,以及保护细胞免受氧化损伤等.对S100蛋白的一般特征、细胞内外的功能及结构的研究进展等方面做了比较全面的阐述.部分S100蛋白三维结构的解析为进一步探讨其功能提供了直观的信息.     

肝素结构与功能的研究进展

肝素是一类结构异常复杂的糖胺聚糖,与此相对应的是其多种生物学功能。除了经典的抗凝血及其相关的抗血栓生成以外,肝素还具有抗平滑肌细胞增殖,抗炎症,抗肿瘤及抗病毒等,并且这些生物活性同抗凝活性无关,而同肝素的特异结构密切相关。     

丙型肝炎病毒核心蛋白结构及功能研究进展

大量研究结果表明丙型肝炎病毒（ＨＣＶ）核心蛋白是多功能蛋白质,它可能与ＨＣＶ致病（癌）有密切关系。本文简述近年来关于核心蛋白结构与功能的最新进展。并初步探讨了ＨＣＶ核心蛋白可能的致病机制。     

IGFBP7基因的结构与功能的研究进展

胰岛素样生长因子结合蛋白7（IGFBP7）是IGFBPs超家族的新成员,结构上除具有与IGFBPs相似的保守N端结构域外,还有特异的Kazal型丝氨酸蛋白酶抑制结构域和免疫球蛋白样C2结构域。除与IGFs结合发挥作用外,还能独立调控细胞凋亡、增殖和迁移等。而至今尚无对水生无脊椎动物IGFBP7的研究报道,结合本实验室的研究综述了目前IGFBP7基因结构和功能上的研究进展,并对今后的研究工作进行了展望。     

One SmpB molecule accompanies tmRNA during its passage through the ribosomes

tmRNA and SmpB are the main participants of trans-translation, a process which rescues the ribosome blocked during translation of non-stop mRNA. While a one-to-one stoichiometry of tmRNA to the ribosome is generally accepted, the number of SmpB molecules in the complex is still under question. We have isolated tmRNA-ribosome complexes blocked at different steps of the tmRNA path through the ribosome and analyzed the stoichiometry of the complexes. Ribosome, tmRNA and SmpB were found in equimolar amount in the tmRNA-ribosome complexes stopped at the position of the 2nd, 4th, 5th or the 11th codons of the coding part of the tmRNA.     

O-linked protein glycosylation structure and function

There has been a recent resurgence of interest in the post-translational modification of serine and threonine hydroxyl groups by glycosylation, because the resulting O-linked oligosaccharide chains tend to be clustered over short stretches of peptide and hence they can present multivalent carbohydrate antigenic or functional determinants for antibody recognition, mammalian cell adhesion and microorganism binding. Co-operativity can greatly increase the affinity of interactions with antibodies or carbohydrate binding proteins. Thus, in addition to their known importance in bearing tumour associated antigens in the gastrointestinal and respiratory tracts, glycoproteins with O-linked chains have been implicated as ligands or co-receptors for selectins (mammalian carbohydrate binding proteins). Microorganisms may have adopted similar mechanisms for interactions with mammalian cells in infection, by having relatively low affinity ligands (adhesins) for carbohydrate binding, which may bind with higher affinity due to the multivalency of the host ligand and which are complemented by other virulence factors such as interactions with integrin-type molecules. In addition to specific adhesion signals from O-linked carbohydrate chains, multivalent O-glycosylation is involved in determining protein conformation and forming conjugate oligosaccharide-protein antigenic, and possible functional determinants.     

寨卡病毒蛋白结构与功能研究进展

2015年以来,南美暴发大规模寨卡疫情,因其与新生儿小头症等严重神经发育疾病密切相关,被世界卫生组织列为国际关注的突发公共卫生事件。与其他虫媒黄病毒类似,寨卡病毒为单股正链RNA病毒,其基因组编码的3种结构蛋白构成病毒颗粒,7种非结构蛋白参与病毒复制生活周期的调控。在全球科学家的共同努力下,寨卡病毒蛋白结构与功能的研究取得了突破性进展,极大地促进研究者对病毒复制与致病机制的认识,也为疫苗和药物研发提供了重要科学依据和潜在靶标。本文将对寨卡病毒蛋白的结构与功能的最新研究进展作一综述,并讨论当前面临的挑战和机遇。     

The role of SmpB protein in trans-translation

The function of SmpB protein in the trans-translation system was evaluated using the well-defined cell-free translation system consisting of purified ribosome, alanyl-tRNA synthetase and elongation factors. The analysis showed that SmpB protein enhances alanine-accepting activity of tmRNA and that SmpB protein and tmRNA are sufficient to complete the trans-translation process in the presence of translational components. Moreover, SmpB is indispensable in the addition of tag-peptide onto ribosomes by tmRNA. In particular, the A-site binding of tmRNA is inhibited in the absence of SmpB.     

tmRNA的结构与功能

tmRNA是一类具有类似tRNA分子和mRNA分子双重功能的小分子RNA,它在一种特殊的翻译模式——反式翻译模式过程中发挥重要作用。最近又发现它与基因的表达调控及细胞周期的调控等生命过程密切相关。因此,关于tmRNA的研究已经引起了研究者的高度重视,它将是RNA组学研究的一个重要内容。文章主要论述了近年来关于tmRNA结构和功能方面的一些研究进展。Abstract: tmRNA is a dual small RNA similar to a tRNA and a mRNA which plays an important role in an unusual mode of translation——trans translation. Recently, it was found that tmRNA had something to do with regulating gene expression and cell cycle. So the researchers have paid much attention on such area. Furthermore, it is an important part in RNomics era. This article reviews the progress about the structure and function of tmRNA in recent years.     

泡沫病毒Gag蛋白的研究进展

Gag蛋白在逆转录病毒复制周期的许多阶段中发挥重要作用。泡沫病毒基因组结构与其它逆转录病毒类似,但它们的基因组成分和生活周期存在明显差异,这在一定程度上是由其Gag蛋白的结构和功能所决定的。本文对18种不同株型的泡沫病毒gag基因序列进行进化树分析,探究不同来源的泡沫病毒的亲缘关系;并以典型的原型泡沫病毒为代表,阐述泡沫病毒Gag蛋白的结构和功能以及对病毒复制不同阶段的影响。     

Unnatural amino acids as probes of protein structure and function

Nonsense suppression methodology, for incorporating unnatural amino acids into proteins, has enabled a wide range of studies into protein structure and function using both in vitro and in vivo translation systems. Although methodological challenges remain, scores of unnatural amino acids have been employed that include both subtle and dramatic variants of the natural set. A number of insights that would not have been possible using conventional site-directed mutagenesis have been gained.     

The role of SmpB and the ribosomal decoding center in licensing tmRNA entry into stalled ribosomes

In bacteria, stalled ribosomes are recycled by a hybrid transfer-messenger RNA (tmRNA). Like tRNA, tmRNA is aminoacylated with alanine and is delivered to the ribosome by EF-Tu, where it reacts with the growing polypeptide chain. tmRNA entry into stalled ribosomes poses a challenge to our understanding of ribosome function because it occurs in the absence of a codon-anticodon interaction. Instead, tmRNA entry is licensed by the binding of its protein partner, SmpB, to the ribosomal decoding center. We analyzed a series of SmpB mutants and found that its C-terminal tail is essential for tmRNA accommodation but not for EF-Tu activation. We obtained evidence that the tail likely functions as a helix on the ribosome to promote accommodation and identified key residues in the tail essential for this step. In addition, our mutational analysis points to a role for the conserved K(131)GKK tail residues in trans-translation after peptidyl transfer to tmRNA, presumably EF-G-mediated translocation or translation of the tmRNA template. Surprisingly, analysis of A1492, A1493, and G530 mutants reveals that while these ribosomal nucleotides are essential for normal tRNA selection, they play little to no role in peptidyl transfer to tmRNA. These studies clarify how SmpB interacts with the ribosomal decoding center to license tmRNA entry into stalled ribosomes.     

A protocol for computer-based protein structure and function prediction

Genome sequencing projects have ciphered millions of protein sequence, which require knowledge of their structure and function to improve the understanding of their biological role. Although experimental methods can provide detailed information for a small fraction of these proteins, computational modeling is needed for the majority of protein molecules which are experimentally uncharacterized. The I-TASSER server is an on-line workbench for high-resolution modeling of protein structure and function. Given a protein sequence, a typical output from the I-TASSER server includes secondary structure prediction, predicted solvent accessibility of each residue, homologous template proteins detected by threading and structure alignments, up to five full-length tertiary structural models, and structure-based functional annotations for enzyme classification, Gene Ontology terms and protein-ligand binding sites. All the predictions are tagged with a confidence score which tells how accurate the predictions are without knowing the experimental data. To facilitate the special requests of end users, the server provides channels to accept user-specified inter-residue distance and contact maps to interactively change the I-TASSER modeling; it also allows users to specify any proteins as template, or to exclude any template proteins during the structure assembly simulations. The structural information could be collected by the users based on experimental evidences or biological insights with the purpose of improving the quality of I-TASSER predictions. The server was evaluated as the best programs for protein structure and function predictions in the recent community-wide CASP experiments. There are currently >20,000 registered scientists from over 100 countries who are using the on-line I-TASSER server.