Solution NMR structure determination of proteins revisited

This 'Perspective' bears on the present state of protein structure determination by NMR in solution. The focus is on a comparison of the infrastructure available for NMR structure determination when compared to protein crystal structure determination by X-ray diffraction. The main conclusion emerges that the unique potential of NMR to generate high resolution data also on dynamics, interactions and conformational equilibria has contributed to a lack of standard procedures for structure determination which would be readily amenable to improved efficiency by automation. To spark renewed discussion on the topic of NMR structure determination of proteins, procedural steps with high potential for improvement are identified.     

Relationships between species diversity or community structure and productivity of woody-plants in a broad-leaved Korean pine forest in Jiaohe,Jilin, China北大核心CSCD

Aims: Based on the dataset of a broad-leaved Korean pine forest in Jiaohe, Jilin Province, this research compared the influences of species diversity and community structure on productivity. We aim to explain the relationship between diversity and productivity for better forest management. Methods: We used the data of 10 973 woody-plants in a 11.76 hm2 large sample plot and analyzed the correlations between 7 different indices of species diversity or community structure and productivity. Structural equation model was used to compare the effects of species diversity and community structure on productivity. Important findings: The results showed that: (1) Both species diversity and community structure had significant effects on productivity when they were considered separately in linear regression analysis, i.e. species evenness was negatively correlated with productivity, the Shannon index of community structure was positively correlated with productivity and the Gini index was negatively correlated with productivity. (2) In the structural equation model, when simultaneously considered, community structure had stronger influence on productivity than species diversity. Our research suggests that, the effects of community structure on productivity are greater than species diversity and it is important to increase community structure complexity to improve forest productivity during forest management.     

Fast structure alignment for protein databank searching.

A fast method is described for searching and analyzing the protein structure databank. It uses secondary structure followed by residue matching to compare protein structures and is developed from a previous structural alignment method based on dynamic programming. Linear representations of secondary structures are derived and their features compared to identify equivalent elements in two proteins. The secondary structure alignment then constrains the residue alignment, which compares only residues within aligned secondary structures and with similar buried areas and torsional angles. The initial secondary structure alignment improves accuracy and provides a means of filtering out unrelated proteins before the slower residue alignment stage. It is possible to search or sort the protein structure databank very quickly using just secondary structure comparisons. A search through 720 structures with a probe protein of 10 secondary structures required 1.7 CPU hours on a Sun 4/280. Alternatively, combined secondary structure and residue alignments, with a cutoff on the secondary structure score to remove pairs of unrelated proteins from further analysis, took 10.1 CPU hours. The method was applied in searches on different classes of proteins and to cluster a subset of the databank into structurally related groups. Relationships were consistent with known families of protein structure.     

Accounting for Population Structure in Gene-by-Environment Interactions in Genome-Wide Association Studies Using Mixed Models

Although genome-wide association studies (GWASs) have discovered numerous novel genetic variants associated with many complex traits and diseases, those genetic variants typically explain only a small fraction of phenotypic variance. Factors that account for phenotypic variance include environmental factors and gene-by-environment interactions (GEIs). Recently, several studies have conducted genome-wide gene-by-environment association analyses and demonstrated important roles of GEIs in complex traits. One of the main challenges in these association studies is to control effects of population structure that may cause spurious associations. Many studies have analyzed how population structure influences statistics of genetic variants and developed several statistical approaches to correct for population structure. However, the impact of population structure on GEI statistics in GWASs has not been extensively studied and nor have there been methods designed to correct for population structure on GEI statistics. In this paper, we show both analytically and empirically that population structure may cause spurious GEIs and use both simulation and two GWAS datasets to support our finding. We propose a statistical approach based on mixed models to account for population structure on GEI statistics. We find that our approach effectively controls population structure on statistics for GEIs as well as for genetic variants.     

蛋白质溶液构象的研究方法

蛋白质的结构决定其功能。研究蛋白质溶液构象的手段日新月异,文章介绍了近年来研究蛋白质在溶液中三级结构、二级结构和基团微环境的常用手段。     

Quaternary structure constraints on evolutionary sequence divergence

The structurally constrained protein evolution (SCPE) model simulates protein divergence considering protein structure explicitly. The model is based on the observation that protein structure is more conserved during evolution than the sequences encoding for that structure. In the previous work, the SCPE model considered only the tertiary structure. Here we show that the performance of the model is enhanced when the oligomeric structure is taken into account. Our results agree with recent evolutionary studies of oligomeric proteins, which show that conservation of the quaternary structure imposes additional constraints on sequence divergence. The incorporation of protein-protein interactions into protein evolution models may be important in the study of quaternary protein structures and complex protein assemblies.     

Prediction of homologous protein structures based on conformational searches and energetics

A "knowledge-based" method of predicting the unknown structure of a protein from a homologous known structure using energetics to determine a sidechain conformation is proposed. The method consists of exchanging the residues in the known structure for the sequence of the unknown protein. Then a conformational search with molecular mechanics energy minimization is done on the exchanged residues. The lowest energy conformer is the one picked to be the predicted structure. In the structure of bovine trypsin, the importance of including a solvation energy term in the search is demonstrated for solvent accessible residues, while molecular mechanics alone is enough to correctly predict the conformation of internal residues. The correctness of the model is assessed by a volume error overlap of the predicted structure compared to the crystal structure. Finally, the structure of rat trypsin is predicted from the crystal structure of bovine trypsin. The sequences of these two proteins are 74% identical and all of the significant changes between them are on external residues. Thus, the inclusion of solvation energy in the conformational search is necessary to accurately predict the structure of the exchanged residues.     

Selective action of acetogenin mitochondrial complex I inhibitors

Five annonaceous acetogenins, rolliniastatin-1 [structure: see text], rolliniastatin-2 [structure: see text], laherradurin [structure: see text], squamocin [structure: see text], annonacin [structure: see text], and rotenone as a reference, differing in their NADH oxidase inhibition activity, have been evaluated for antifeedant, insecticidal, trypanocidal and cytotoxic effects on insect, mammalian and tumor cells. All the test compounds were toxic to Leptinotarsa decemlineata, demonstrated selective cytotoxicity to insect Sf9 cells and a panel of tumor cell lines with the multidrug-resistant SW480 (P-glycoprotein+, Pgp+) being the most sensitive one. Compounds [structure: see text] and rotenone had post-ingestive effects against Spodoptera littoralis larvae while [structure: see text] and rotenone were active against Trypanosoma cruzi. Based on their biochemical properties (inhibition of the mitochondrial NADH oxidase activity), the in vivo effects of these compounds on S. littoralis and their cytotoxic effects on Sf9 and tumor cells were more predictable than their effect on T. cruzi and mammalian cells.     

农田防护林生态系统结构研究进展

农田防护林生态系统结构决定着生态功能,其时空结构是该领域研究的核心,旨在探讨形成结构的完整性、稳定性、持久性的组件间的相互关系,将其分为树体结构、林带结构、林网结构、景观结构4个层次,针对各层次中结构研究的原理、方法及成果进行了综述,通过树木个体的形态、质态结构研究,应用分形图形学的手段可实现动态结构的可视化,以研究林带树体结构的生成机理;精确界定林带结构的分维疏透度。探讨农田防护林带最佳结构理论,以构建防护林带最佳结构计算机生成模型;确立多物种、多层次的窄林带小网格的林网优化模式;评价农田防护林景观的合理性、稳定性、持续性,是今后的重要研究方向。     

植物群落中物种小尺度空间结构研究

植物群落中, 物种小尺度空间结构影响着种群或群落的动态及有关的生态学过程。植物主要是和它同种或异种的邻近个体相互作用,植物个体周围的局部环境和大空间尺度下群落的平均水平是完全不同的。群落中的许多过程都影响小尺度空间结构的形成和动态,同样,局部空间结构反过来影响着植物的生长、更新和凋亡等重要过程。鉴于目前对小尺度空间结构进行的大量研究以及其重要性,有必要对其研究进展进行适当的总结,以期明确将来进一步的研究方向。该文以此为出发点,首先介绍了植物群落中物种小尺度空间结构产生的6个原因:1)生境的空间异质性;2)植物繁殖体的传播;3)植物之间的相互作用;4)生物环境(动物和微生物)的作用;5)外界干扰的作用;6)多因子综合作用。然后阐述了小尺度空间结构意义及对生物多样性、植物种群遗传学和恢复生态学研究的影响。最后对目前物种小尺度空间结构研究存在的几点问题及将来的研究方向作以下归纳:1)大尺度植被动态的研究应该整合小尺度空间结构的信息;2)不论从生物学还是生态学上来讲, 植被小尺度空间结构的研究应该把植物作为中心,确定适当的尺度和采取合理的空间统计方法;3)充分重视小尺度空间结构在退化生态系统恢复中的应用意义;4)注重从小尺度的局部格局研究入手对群落总体特征进行整合;5)植物群落动态研究中,物种小尺度空间结构与平均场假说相结合的必要性。     

综述: 30 nm染色质纤维的结构及调控

真核细胞中,基因组DNA缠绕组蛋白八聚体形成核小体,核小体再经过多层次折叠压缩形成具有高级结构的染色质．过去30多年,科学家对30 nm染色质纤维的结构进行了大量的研究,然而关于30 nm染色质纤维的精细结构仍然存在很大的争议．本文综述了近年来对30 nm染色质纤维结构的最新研究进展,并重点阐述了最近解析的30 nm染色质纤维左 手双螺旋结构．同时,我们还进一步讨论了一些对30 nm染色质纤维结构起调控作用的因子及其作用机制．最后,我们对30 nm染色质纤维结构与功能领域所面临的挑战和问题进行了展望．     

Hydrography and population genetic structure in brook charr (Salvelinus fontinalis, Mitchill) from eastern Canada

Despite the abundance of studies of genetic diversity in freshwater fishes, few have specifically addressed the role of habitat structure in partitioning genetic variance within and among populations. In this study, we analysed the variability of six microsatellite loci among 24 brook charr population samples in order to correlate hydrographic structure with genetic organization. These populations originated from three Canadian National parks (Kouchibouguac, Fundy and Forillon) that showed distinct hydrographic structure. Considering the general characteristics of these habitats, we formulated specific hypotheses in regard to genetic structure, which were principally based on the potential for gene flow and population size associated with each habitat. The hierarchical analysis of molecular variance and the genetic distances computed among populations revealed that habitat structure analyses constitute an important, but insufficient, predictor of genetic structure. We discuss the importance of habitat complexity on genetic structure in the context of management and conservation.     

融入植被结构因子的生态单元制图法在城市生物多样性信息采集中的应用

以前所使用的生态单元制图模型中没有涉及植被时间和空间结构因子,然而一些研究结果显示植被的时空结构对于生物多样性有着重要的影响。因此,设计一个融入植被结构因子的改良城市生态单元制图模型,并且将其应用于瑞典赫尔辛堡市的绿色空间个案研究中,以期能够获得有关生物多样性方面的信息。这个改良的制图方法基于一个生态单元分类系统,此分类系统融入了4个植被结构因子,分别是:植被覆盖的连续性因子、优势乔木种的年龄因子、横向结构因子以及竖向结构因子。公共绿色空间信息的采集借助于全彩色航空照片的分析以及实地调查,生态单元图谱的绘制基于各个层级的生态单元分类重点。通过使用原生林地指示种或林地连续性指示种(AWIS)鉴定林地的连续性以及观测不同的植被结构下动物的分布情况得出,一些含有AWIS的生态单元是长连续性的林地,并且其含有较高的或潜在高的生物多样性;同时,植被的横向和竖向结构以及树木的年龄结构影响着鸟类和哺乳动物的分布、丰富度和多样性。得出融入植被时空结构的生态单元制图法是一个重要的调查城市生物多样性的方法,图谱能够显示出各个生态单元含有生物多样性价值的信息,基于此可以对今后的城市生物多样性保护和提高提出相应的策略。     

Selection of Statistical Thresholds in Graphical Models

Reconstruction of gene regulatory networks based on experimental data usually relies on statistical evidence, necessitating the choice of a statistical threshold which defines a significant biological effect. Approaches to this problem found in the literature range from rigorous multiple testing procedures to ad hoc P-value cut-off points. However, when the data implies graphical structure, it should be possible to exploit this feature in the threshold selection process. In this article we propose a procedure based on this principle. Using coding theory we devise a measure of graphical structure, for example, highly connected nodes or chain structure. The measure for a particular graph can be compared to that of a random graph and structure inferred on that basis. By varying the statistical threshold the maximum deviation from random structure can be estimated, and the threshold is then chosen on that basis. A global test for graph structure follows naturally.     

Nobel lecture. The photosynthetic reaction centre from the purple bacterium Rhodopseudomonas viridis.

In our lectures we first describe the history and methods of membrane protein crystallization, before we show how the structure of the photosynthetic reaction centre from the purple bacterium Rhodopseudomonas viridis was solved. Then the structure of this membrane protein complex is correlated with its function as a light-driven electron pump across the photosynthetic membrane. Finally we draw conclusions on the structure of the photosystem II reaction centre from plants and discuss the aspects of membrane protein structure. Sections 1 (crystallization), 4 (conclusions on the structure of photosystem II reaction centre and evolutionary aspects) and 5 (aspects of membrane protein structure) were presented and written by H.M., Sections 2 (determination of the structure) and 3 (structure and function) by J.D. We have arranged the paper in this way in order to facilitate continuous reading.     

Prediction of the tertiary structure of the alpha-subunit of tryptophan synthase

The tertiary structure of the alpha-subunit of tryptophan synthase was proposed using a combination of experimental data and computational methods. The vacuum-ultraviolet circular dichroism spectrum was used to assign the protein to the alpha/beta-class of supersecondary structures. The two-domain structure of the alpha-subunit (Miles et al.: Biochemistry 21:2586, 1982; Beasty and Matthews: Biochemistry 24:3547, 1985) eliminated consideration of a barrel structure and focused attention on a beta-sheet structure. An algorithm (Cohen et al.: Biochemistry 22:4894, 1983) was used to generate a secondary structure prediction that was consistent with the sequence data of the alpha-subunit from five species. Three potential secondary structures were then packed into tertiary structures using other algorithms. The assumption of nearest neighbors from second-site revertant data eliminated 97% of the possible tertiary structures; consideration of conserved hydrophobic packing regions on the beta-sheet eliminated all but one structure. The native structure is predicted to have a parallel beta-sheet flanked on both sides by alpha-helices, and is consistent with the available data on chemical cross-linking, chemical modification, and limited proteolysis. In addition, an active site region containing appropriate residues could be identified as well as an interface for beta 2-subunit association. The ability of experimental data to facilitate the prediction of protein structure is discussed.     

Strong influence of regional species pools on continent-wide structuring of local communities

There is a long tradition in ecology of evaluating the relative contribution of the regional species pool and local interactions on the structure of local communities. Similarly, a growing number of studies assess the phylogenetic structure of communities, relative to that in the regional species pool, to examine the interplay between broad-scale evolutionary and fine-scale ecological processes. Finally, a renewed interest in the influence of species source pools on communities has shown that the definition of the source pool influences interpretations of patterns of community structure. We use a continent-wide dataset of local ant communities and implement ecologically explicit source pool definitions to examine the relative importance of regional species pools and local interactions for shaping community structure. Then we assess which factors underlie systematic variation in the structure of communities along climatic gradients. We find that the average phylogenetic relatedness of species in ant communities decreases from tropical to temperate regions, but the strength of this relationship depends on the level of ecological realism in the definition of source pools. We conclude that the evolution of climatic niches influences the phylogenetic structure of regional source pools and that the influence of regional source pools on local community structure is strong.     

Relationships between species diversity or community structure and productivity of woody-plants in a broad-leaved Korean pine forest in Jiaohe,Jilin, China

Aims Based on the dataset of a broad-leaved Korean pine forest in Jiaohe, Jilin Province, this research compared the influences of species diversity and community structure on productivity. We aim to explain the relationship between diversity and productivity for better forest management. Methods We used the data of 10 973 woody-plants in a 11.76 hm² large sample plot and analyzed the correlations between 7 different indices of species diversity or community structure and productivity. Structural equation model was used to compare the effects of species diversity and community structure on productivity. Important findings The results showed that: (1) Both species diversity and community structure had significant effects on productivity when they were considered separately in linear regression analysis, i.e. species evenness was negatively correlated with productivity, the Shannon index of community structure was positively correlated with productivity and the Gini index was negatively correlated with productivity. (2) In the structural equation model, when simultaneously considered, community structure had stronger influence on productivity than species diversity. Our research suggests that, the effects of community structure on productivity are greater than species diversity and it is important to increase community structure complexity to improve forest productivity during forest management.     

MMDB: Entrez's 3D-structure database

Three-dimensional structures are now known within most protein families and it is likely, when searching a sequence database, that one will identify a homolog of known structure. The goal of Entrez's 3D-structure database is to make structure information and the functional annotation it can provide easily accessible to molecular biologists. To this end, Entrez's search engine provides several powerful features: (i) links between databases, for example between a protein's sequence and structure; (ii) pre-computed sequence and structure neighbors; and (iii) structure and sequence/structure alignment visualization. Here, we focus on a new feature of Entrez's Molecular Modeling Database (MMDB): Graphical summaries of the biological annotation available for each 3D structure, based on the results of automated comparative analysis. MMDB is available at: http://www.ncbi.nlm.nih.gov/Entrez/structure.html.