The structure of DNA in the nucleosome core

The 1.9-A-resolution crystal structure of the nucleosome core particle containing 147 DNA base pairs reveals the conformation of nucleosomal DNA with unprecedented accuracy. The DNA structure is remarkably different from that in oligonucleotides and non-histone protein-DNA complexes. The DNA base-pair-step geometry has, overall, twice the curvature necessary to accommodate the DNA superhelical path in the nucleosome. DNA segments bent into the minor groove are either kinked or alternately shifted. The unusual DNA conformational parameters induced by the binding of histone protein have implications for sequence-dependent protein recognition and nucleosome positioning and mobility. Comparison of the 147-base-pair structure with two 146-base-pair structures reveals alterations in DNA twist that are evidently common in bulk chromatin, and which are of probable importance for chromatin fibre formation and chromatin remodelling.     

DNA证据审查初探

审查DNA证据就是对其科学可靠性进行评断,以确定其有无证明力及证明力的大小,这在诉讼活动中是必要的,且已被赋予了法律地位。DNA证据审查可从如下环节入手:DNA样本发现、提取和保管环节,证据合法环节,DNA检验环节,结果解释环节,与案件有利害关系人员回避环节。     

Protein folding in the cell.

In the cell, as in vitro, the final conformation of a protein is determined by its amino-acid sequence. But whereas some isolated proteins can be denatured and refolded in vitro in the absence of other macromolecular cellular components, folding and assembly of polypeptides in vivo involves other proteins, many of which belong to families that have been highly conserved during evolution.     

预测蛋白质折叠结构的剪枝算法

为求解蛋白质折叠结构预测问题提出一种基于剪枝策略的启发式搜索算法.剪枝算法用一棵搜索树描述蛋白质构形的生长过程,通过定义权重、上下门槛制定一套有效的控制分支繁殖的规则,从而极大地提高了搜索的效率.采用国际文献公认的10个算例作为剪枝算法的实验测试集,并与目前国际上4个著名的算法进行比较,实验比较结果表明剪枝算法是一个高效的求解算法.     

Mixed search algorithm for protein folding

0　IntroductionThedeterminationofthefoldingpathwayfollowedbyaproteinintheconformationalspacefromthedenaturedstatetothenativestructureisstillanunsolvedproblem .Itsdifficultyismainlyduetotheenormousextensionoftheconformationalspaceandtoitsexponentialgrowthwhenthelengthoftheproteinchainincreases.HowaproteinsolvestheLevinthalparadox[1 ] ,i.e.,howitfoldstoitsnativestructurewithoutanexhaustivesearchintheconforma tionalspace,hasbeenlargelydebatedinRef.[2 5 ].Thenatureofthedrivingforcesinducingtheco…     

Determinants of nucleosome organization in primary human cells

Nucleosomes are the basic packaging units of chromatin, modulating accessibility of regulatory proteins to DNA and thus influencing eukaryotic gene regulation. Elaborate chromatin remodelling mechanisms have evolved that govern nucleosome organization at promoters, regulatory elements, and other functional regions in the genome. Analyses of chromatin landscape have uncovered a variety of mechanisms, including DNA sequence preferences, that can influence nucleosome positions. To identify major determinants of nucleosome organization in the human genome, we used deep sequencing to map nucleosome positions in three primary human cell types and in vitro. A majority of the genome showed substantial flexibility of nucleosome positions, whereas a small fraction showed reproducibly positioned nucleosomes. Certain sites that position in vitro can anchor the formation of nucleosomal arrays that have cell type-specific spacing in vivo. Our results unveil an interplay of sequence-based nucleosome preferences and non-nucleosomal factors in determining nucleosome organization within mammalian cells.     

Crystal structure of the human centromeric nucleosome containing CENP-A

In eukaryotes, accurate chromosome segregation during mitosis and meiosis is coordinated by kinetochores, which are unique chromosomal sites for microtubule attachment. Centromeres specify the kinetochore formation sites on individual chromosomes, and are epigenetically marked by the assembly of nucleosomes containing the centromere-specific histone H3 variant, CENP-A. Although the underlying mechanism is unclear, centromere inheritance is probably dictated by the architecture of the centromeric nucleosome. Here we report the crystal structure of the human centromeric nucleosome containing CENP-A and its cognate α-satellite DNA derivative (147 base pairs). In the human CENP-A nucleosome, the DNA is wrapped around the histone octamer, consisting of two each of histones H2A, H2B, H4 and CENP-A, in a left-handed orientation. However, unlike the canonical H3 nucleosome, only the central 121 base pairs of the DNA are visible. The thirteen base pairs from both ends of the DNA are invisible in the crystal structure, and the αN helix of CENP-A is shorter than that of H3, which is known to be important for the orientation of the DNA ends in the canonical H3 nucleosome. A structural comparison of the CENP-A and H3 nucleosomes revealed that CENP-A contains two extra amino acid residues (Arg?80 and Gly?81) in the loop 1 region, which is completely exposed to the solvent. Mutations of the CENP-A loop 1 residues reduced CENP-A retention at the centromeres in human cells. Therefore, the CENP-A loop 1 may function in stabilizing the centromeric chromatin containing CENP-A, possibly by providing a binding site for trans-acting factors. The structure provides the first atomic-resolution picture of the centromere-specific nucleosome.     

求解蛋白质折叠问题的改进PERM算法

在学习PERM算法的基础上，指出了影响PERM算法效率的关键因素，进而提出了一种改进的PERM算法——IPERM(Improved PERM)．计算结果表明，IPERM的计算效率优于PERM算法，并且远高于基于蒙特卡罗的MSOE算法和基于重要性抽样的SISPER算法．     

Evidence for fixed charge in the nexus

The nexus or gap junction has been characterized as a low-resistance junction as well as a highly permeable junctional membrane to many molecules. The transfer of electrical current from one cell interior to another, the aqueous solubility of dyes used to trace cell to cell communication and the fact that these molecules move across the nexus more rapidly than the plasma membrane have led to the hypothesis of an aqueous channel in the junction. Both Ca2+ (ref.11) and H+ (ref. 12) are thought to alter nexal membrane conductance, and a voltage-sensitive gate has been demonstrated within the junction. Recently, Flagg-Newton et al. have concluded that mammalian junctions may contain fixed charge or be of smaller diameter than arthropod junctions. Here we have investigated these alternatives by examining the permeability of nexuses of septa of the median giant axon of Lumbricus terrestris with various derivatives of fluorescein. Both carboxyfluorescein and aminofluorescein were found to have depressed permeabilities relative to their predicted permeabilities based on molecular size and weight (MW). Flourescein diffusion was significantly suppressed in axons pre-injected with aminofluorescein but carboxyfluorescein had no such effect (Table 1). These data suggest the existence of fixed anionic charge within the nexal channel which may have affinity for amino groups.     

Requirement for hsp70 in the mitochondrial matrix for translocation and folding of precursor proteins

By analysis of a temperature-sensitive yeast mutant, a heat-shock protein in the matrix of mitochondria, mitochondrial hsp70 (Ssc1p), is found to be involved both in translocation of nuclear-encoded precursor proteins across the mitochondrial membranes and in (re)folding of imported proteins in the matrix.     

Personification algorithm for protein folding problem：Improvements in PERM

PERM is the most efficient approach for solving protein folding problem based on simple lattice model. In this article a personification explanation of PERM is proposed. A new version of PERM, population control algorithm with two main improvements is presented: one is that it is able to redefine the weight and its predicted value in PERM,and the other is that it is able to unify the calculation of weight when choosing possible branches. The improved PERM is more efficient than the previous version; specifically it can find the known lowest energy states for the four well-known difficult instances and is generally several to hundreds times faster than PERM. It is noteworthy that with the improved PERM we found new lowest energy configurations of three of the four difficult problems missed in previous papers.