分类： 生物学 >> 生物物理学 提交时间： 2016-05-12
摘要： The prokaryotic mechanosensitive channel of large conductance (MscL) is a pressure-relief valve protecting the cell from lysing during acute osmotic downshock. When the membrane is stretched, MscL responds to the increase of membrane tension and opens a nonselective pore to about 30 angstrom wide, exhibiting a large unitary conductance of similar to 3 nS. A fundamental step toward understanding the gating mechanism of MscL is to decipher the molecular details of the conformational changes accompanying channel opening. By applying fusion-protein strategy and controlling detergent composition, we have solved the structures of an archaeal MscL homolog from Methanosarcina acetivorans trapped in the closed and expanded intermediate states. The comparative analysis of these two new structures reveals significant conformational rearrangements in the different domains of MscL. The large changes observed in the tilt angles of the two transmembrane helices (TM1 and TM2) fit well with the helix-pivoting model derived from the earlier geometric analyses based on the previous structures. Meanwhile, the periplasmic loop region transforms from a folded structure, containing an.-shaped loop and a short beta-hairpin, to an extended and partly disordered conformation during channel expansion. Moreover, a significant rotating and sliding of the N-terminal helix (N-helix) is coupled to the tilting movements of TM1 and TM2. The dynamic relationships between the N-helix and TM1/TM2 suggest that the N-helix serves as a membrane-anchored stopper that limits the tilts of TM1 and TM2 in the gating process. These results provide direct mechanistic insights into the highly coordinated movement of the different domains of the MscL channel when it expands.
分类： 医学、药学 >> 临床医学 提交时间： 2023-11-10 合作期刊: 《中国全科医学》
摘要： none
分类： 生物学 >> 生态学 提交时间： 2023-05-11 合作期刊: 《干旱区科学》
摘要：Ecosystem responses to climate change, particularly in arid environments, is an understudied topic. This study conducted a spatial analysis of ecosystem responses to short-term variability in temperature, precipitation, and solar radiation in the Qilian Mountains National Park, an arid mountainous region in Northwest China. We collected precipitation and temperature data from the National Science and Technology Infrastructure Platform, solar radiation data from the China Meteorological Forcing Dataset, and vegetation cover remote-sensing data from the Moderate Resolution Imaging Spectroradiometer. We used the vegetation sensitivity index to identify areas sensitive to climate change and to determine which climatic factors were significant in this regard. The findings revealed a high degree of heterogeneity and non-linearity of ecosystem responses to climate change. Four types of heterogeneity were identified: longitude, altitude, ecosystem, and climate disturbance. Furthermore, the characteristics of nonlinear ecosystem responses to climate change included: (1) inconsistency in the controlling climatic factors for the same ecosystems in different geographical settings; (2) the interaction between different climatic factors results in varying weights that affect ecosystem stability and makes them difficult to determine; and (3) the hysteresis effect of vegetation increases the uncertainty of ecosystem responses to climate change. The findings are significant because they highlight the complexity of ecosystem responses to climate change. Furthermore, the identification of areas that are particularly sensitive to climate change and the influencing factors has important implications for predicting and managing the impacts of climate change on ecosystems, which can help protect the stability of ecosystems in the Qilian Mountains National Park.
分类： 医学、药学 >> 基础医学 提交时间： 2017-12-27 合作期刊: 《南方医科大学学报》
摘要： Objective To investigate the protective effects of tea polyphenols (TP) against myocardial ischemia/reperfusion (IR) injuries and explore the possible mechanisms. Methods Langendorff-perfused rat hearts were subjected to ischemia for 30 min followed by reperfusion for another 30 min. Myocardial function indices were measured by a left ventricular cannula via a pressure transducer connected to the polygraph in isolated Langendorff hearts and energy metabolism was measured using 31P nuclear magnetic resonance (NMR) spectroscopy. Whole-cell patch-clamp technique was used to record calcium inward current (ICa-L) in cultured rat cardiac myocytes. Results Compared with the control hearts, the ex vivo rat hearts with 2.5 mg/L TP treatment showed significantly increased left ventricular developed pressure (LVDP), maximal rise rate of LVDP (+ dp/dtmax), maximal fall rate of LVDP (-dp/dtmax), and coronary flow (CF) (P<0.05). During both cardiac ischemia and reperfusion phase, ATP and PCr levels were elevated significantly in TP-treated hearts compared with those in the control hearts (P<0.05). In cultured rat cardiac myocytes, ICa-L was remarkably decreased by TP at the doses of 2.5 and 5.0 mg/L (P<0.01). Conclusion Our results support a possible protective role of TP against myocardial IR injury by improving myocardial energy metabolism and inhibiting ICa-L in the cardiac myocytes.
分类： 生物学 >> 生物物理学 提交时间： 2016-05-11
Guo, Xue
Wang, Ling
Li, Jie
Xiao, Jianxiong
Yin, Xiaotong
He, Shuang
Xu, Yanhui
Guo, Xue
Wang, Ling
Xu, Yanhui
Ding, Zhanyu
Cong, Yao
Shi, Pan
Tian, Changlin
Shi, Pan
Tian, Changlin
Shi, Pan
Tian, Changlin
Dong, Liping
Li, Guohong
摘要： DNA methylation is an important epigenetic modification that is essential for various developmental processes through regulating gene expression, genomic imprinting, and epigenetic inheritance(1-5). Mammalian genomic DNA methylation is established during embryogenesis by de novo DNA methyltransferases, DNMT3A and DNMT3B(6-8), and the methylation patterns vary with developmental stages and cell types(9-12). DNAmethyltransferase 3-like protein (DNMT3L) is a catalytically inactive paralogue of DNMT3 enzymes, which stimulates the enzymatic activity of Dnmt3a(13). Recent studies have established a connection between DNA methylation and histone modifications, and revealed a histone-guided mechanism for the establishment of DNA methylation(14). The ATRX-DNMT3-DNMT3L (ADD) domain of Dnmt3a recognizes unmethylated histone H3 (H3K4me0)(15-17). The histone H3 tail stimulates the enzymatic activity of Dnmt3a in vitro(17,18), whereas the molecular mechanism remains elusive. Here we show that DNMT3A exists in an autoinhibitory form and that the histone H3 tail stimulates its activity in a DNMT3L-independent manner. We determine the crystal structures of DNMT3A-DNMT3L (autoinhibitory form) and DNMT3A-DNMT3L-H3 (active form) complexes at 3.82 and 2.90 angstrom resolution, respectively. Structural and biochemical analyses indicate that the ADD domain of DNMT3A interacts with and inhibits enzymatic activity of the catalyticdomain (CD) through blocking its DNA-binding affinity. HistoneH3(but not H3K4me3) disrupts ADD-CD interaction, induces a large movement of the ADD domain, and thus releases the autoinhibition of DNMT3A. The finding adds another layer of regulation of DNA methylation to ensure that the enzyme is mainly activated at proper targeting loci when unmethylated H3K4 is present, and strongly supports a negative correlation between H3K4me3 and DNA methylation across the mammalian genome(9,10,19,20). Our study provides a new insight into an unexpected autoinhibition and histone H3-induced activation of the de novo DNA methyltransferase after its initial genomic positioning.
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