To understand how the stabilities of key nuclei fragments affect protein folding dynamics, we simulate by molecular dynamics （MD） simulation in aqueous solution four fragments cut out of a protein G, including one a...To understand how the stabilities of key nuclei fragments affect protein folding dynamics, we simulate by molecular dynamics （MD） simulation in aqueous solution four fragments cut out of a protein G, including one a-helix （seqB： KVFKQYAN）, two -turns （seqA： LNGKTLKG and seqC： YDDATKTF）, and one -strand （seqD： DGEWTYDD）. The Markov State Model clustering method combined with the coarse-grained conformation letters method are employed to analyze the data sampled from 2-#s equilibrium MD simulation trajectories. We find that seqA and seqB have more stable structures than their native structures which become metastable when cut out of the protein structure. As expected, seqD alone is flexible and does not have a stable structure. Throughout our simulations, the native structure of seqC is stable but cannot be reached if starting from a structure other than the native one, implying a funnel-shape free energy landscape of seqC in aqueous solution. All the above results suggest that different nuclei have different formation dynamics during protein folding, which may have a major contribution to the hierarchy of protein folding dynamics.展开更多
Epigenetic processes are important mechanisms for phenotypic changes that occur in response to the environment. As such, it is expected that the alteration of cytoplasmic composition （the immediate environment of nuc...Epigenetic processes are important mechanisms for phenotypic changes that occur in response to the environment. As such, it is expected that the alteration of cytoplasmic composition （the immediate environment of nuclei） results in the modifica- tion of the methylome and the expression of the nuclear genome. Cytoplasmic hybrids （or cybrids） are an ideal model to study the influence of mitochondria on gene expression. In this study, we take advantage of the natural of two biotypes that have a similar nuclear genome type Chrosomus eos, but harbor mitochondria from different species （C. eos in wild type or C. neogaeus in cybrids） to assess the effects of mitochondria on DNA methylation profiles and protein expression of the nuclear ge- nome. Comparison between these biotypes is particularly relevant given their recent divergence and their low level of genetic dif- ferentiation. Variations of DNA methylation assessed on tissues from different embryonic origins revealed the distinct profiles of cybrid and wild type populations. Differences are more pronounced between wild type and cybrids than between populations of a given biotype. The proteome is also more different between biotypes than within a given biotype. These results indicate a strong influence of mitochondria on the nuclear genome, which remains detectable in different genetic and environmental contexts. These changes in the methylome and proteome of cybrids are expected to reflect the adjustments imposed by the coexistence of nuclear and mitochondrial genomes from different species [Current Zoology 58 （1）： 138-145, 2012].展开更多
基金Supported by the National Basic Research Program of China under Grant No.2013CB932804the National Natural Science Foundation of China under Grant No.11421063the CAS Biophysics Interdisciplinary Innovation Team Project
文摘To understand how the stabilities of key nuclei fragments affect protein folding dynamics, we simulate by molecular dynamics （MD） simulation in aqueous solution four fragments cut out of a protein G, including one a-helix （seqB： KVFKQYAN）, two -turns （seqA： LNGKTLKG and seqC： YDDATKTF）, and one -strand （seqD： DGEWTYDD）. The Markov State Model clustering method combined with the coarse-grained conformation letters method are employed to analyze the data sampled from 2-#s equilibrium MD simulation trajectories. We find that seqA and seqB have more stable structures than their native structures which become metastable when cut out of the protein structure. As expected, seqD alone is flexible and does not have a stable structure. Throughout our simulations, the native structure of seqC is stable but cannot be reached if starting from a structure other than the native one, implying a funnel-shape free energy landscape of seqC in aqueous solution. All the above results suggest that different nuclei have different formation dynamics during protein folding, which may have a major contribution to the hierarchy of protein folding dynamics.
文摘Epigenetic processes are important mechanisms for phenotypic changes that occur in response to the environment. As such, it is expected that the alteration of cytoplasmic composition （the immediate environment of nuclei） results in the modifica- tion of the methylome and the expression of the nuclear genome. Cytoplasmic hybrids （or cybrids） are an ideal model to study the influence of mitochondria on gene expression. In this study, we take advantage of the natural of two biotypes that have a similar nuclear genome type Chrosomus eos, but harbor mitochondria from different species （C. eos in wild type or C. neogaeus in cybrids） to assess the effects of mitochondria on DNA methylation profiles and protein expression of the nuclear ge- nome. Comparison between these biotypes is particularly relevant given their recent divergence and their low level of genetic dif- ferentiation. Variations of DNA methylation assessed on tissues from different embryonic origins revealed the distinct profiles of cybrid and wild type populations. Differences are more pronounced between wild type and cybrids than between populations of a given biotype. The proteome is also more different between biotypes than within a given biotype. These results indicate a strong influence of mitochondria on the nuclear genome, which remains detectable in different genetic and environmental contexts. These changes in the methylome and proteome of cybrids are expected to reflect the adjustments imposed by the coexistence of nuclear and mitochondrial genomes from different species [Current Zoology 58 （1）： 138-145, 2012].
