Western Superconducting Technologies Co. Ltd. (WST) has been keeping in the research and development of internal-Tin NbSn strand for higher performance level, for the future fusion reactor after ITER. Deformation optimization, Cu splits, and Sn spacers were applied to prepare NbSn strand with higher J{{\rm{cn}}} and lower hysteresis loss, and the effect of these three factors on performance was investigated and discussed. Compared with the NbSn strand for ITER, strand distortion was obviously reduced by deformation optimization and J{{\rm{cn}}} was improved, but at the same time hysteresis level was increased. To reduce the level of hysteresis loss, Cu splits were used to replace a few Nb filaments in each subelement. Cu splits could break the bridging NbSn filament rings and as a sequence hysteresis loss was dramatically reduced along with the reduction of J{{\rm{cn}}}, which is attributed to low reaction degree of Nb filaments in the outermost subelements. Therefore, Sn spacers between the outermost subelements and the Ta barrier were added, and a 37-subelement structure was used to shorten the diffusion path of Sn. The reaction degree of the filaments was enhanced as well as J{{\rm{cn}}}. Finally, it could be concluded that a 37-subelement structure with Cu splits is effective to reduce the level of hysteresis loss and raise the level of J.

Liu    施一公     Wu Bo    Zhang    Li    Liu Xianghong    Feng Yong    Zhang Pingxiang   

IEEE Transactions on Applied Superconductivity

2018

Pre-mRNA splicing is executed by the ribonucleoprotein machinery spliceosome. Nearly 40 years after the discovery of pre-mRNA splicing, the atomic structure of the spliceosome has finally come to light. Four distinct conformational states of the yeast spliceosome have been captured at atomic or near-atomic resolutions. Two catalytic metal ions at the active site are specifically coordinated by the U6 small nuclear RNA (snRNA) and catalyze both the branching reaction and the exon ligation. Of the three snRNAs in the fully assembled spliceosome, U5 and U6, along with 30 contiguous nucleotides of U2 at its 5'-end, remain structurally rigid throughout the splicing reaction. The rigidity of these RNA elements is safeguarded by Prp8 and 16 core protein components, which maintain the same overall conformation in all structurally characterized spliceosomes during the splicing reaction. Only the sequences downstream of nucleotide 30 of U2 snRNA are mobile; their movement, directed by the protein components, delivers the intron branch site into the close proximity of the 5'-splice site for the branching reaction. A set of additional structural rearrangement is required for exon ligation, and the lariat junction is moved out of the active site for recruitment of the 3'-splice site and 3'-exon. The spliceosome is proven to be a protein-directed metalloribozyme.

施一公    

Journal of Molecular Biology

2017

Intramembrane proteases catalyze hydrolysis of peptide bond within the lipid bilayer and play a key role in a variety of cellular processes. These membrane-embedded enzymes comprise four major classes: rhomboid serine proteases, site-2 metalloproteases, Rce1-type glutamyl proteases, and aspartyl proteases exemplified by signal peptide peptidase and γ-secretase. In the past several years, three-dimensional structures of representative members of these four classes of intramembrane protease have been reported at atomic resolutions, which reveal distinct protein folds and active site configurations. These structures, together with structure-guided biochemical analyses, shed light on the working mechanisms of water access and substrate entry. In this review, we discuss the shared as well as unique features of these intramembrane proteases, with a focus on presenilin - the catalytic component of γ-secretase.

孙林峰    Xiaochun Li    施一公    

Current Opinion in Structural Biology

2016

Splicing of precursor messenger RNA is accomplished by a dynamic megacomplex known as the spliceosome. Assembly of a functional spliceosome requires a preassembled U4/U6.U5 tri-snRNP complex, which comprises the U5 small nuclear ribonucleoprotein (snRNP), the U4 and U6 small nuclear RNA (snRNA) duplex, and a number of protein factors. Here we report the three-dimensional structure of a Saccharomyces cerevisiae U4/U6.U5 tri-snRNP at an overall resolution of 3.8 angstroms by single-particle electron cryomicroscopy. The local resolution for the core regions of the tri-snRNP reaches 3.0 to 3.5 angstroms, allowing construction of a refined atomic model. Our structure contains U5 snRNA, the extensively base-paired U4/U6 snRNA, and 30 proteins including Prp8 and Snu114, which amount to 8495 amino acids and 263 nucleotides with a combined molecular mass of 1 megadalton. The catalytic nucleotide U80 from U6 snRNA exists in an inactive conformation, stabilized by its base-pairing interactions with U4 snRNA and protected by Prp3. Pre-messenger RNA is bound in the tri-snRNP through base-pairing interactions with U6 snRNA and loop I of U5 snRNA. This structure, together with that of the spliceosome, reveals the molecular choreography of the snRNAs in the activation process of the spliceosomal ribozyme.

万蕊雪    Yan Chuangye    Bai Rui    Wang Lin    Huang Min    Wong Catherine C. L.    施一公    

Science

2016

Three kinds of NbSn strands with different designs were made by bronze route. Studies were carried out on bronze-to-NbTa-volume ratio, filament diameter, annealing, hot isostatic pressure process, diffusion barrier, and heat treatment. It is important for strand designs to achieve a good performance. Moreover, bronze-to-NbTa-volume ratios of 2.4 and 2.8 were applied in the strand designs. Strands with lower bronze ratio means that more NbSn layer fraction formed, while, at the same time, it is provided with a high critical current density (J). J increases with the reduction of filament diameter, when there is the same bronze ratio. In addition, Nb and Ta were used as diffusion barrier materials. A strand that used Nb barrier has several times hysteresis loss to a strand that used Ta barrier. When it comes to the intermediate processes, such as annealing and hot isostatic pressure, they could affect the homogeneous deformation and properties of strands. It is important to keep a low annealing temperature to realize a high J and n-value. As for the hot isostatic pressure process, it is helpful for uniform cross section. Furthermore, different heat treatments were also carried out, while analysis was also conducted on the microstructure.

Zhang Ke    Zhang Pingxiang    Guo    Jia    施一公     Liu    Gao Huixian    Li    Liu Xianghong    Feng Yong   

IEEE Transactions on Applied Superconductivity

2016

ITER toroidal field (TF) systems consist of 18 independent coils that are around the torus, whose primary function is to confine the plasma particles. The TF coil conductor is a cable-in-conduit conductor (CICC) made up of superconducting, NbSn-based strands mixed with pure copper strands. As the only supplier in China, Western Superconducting Technologies Company, Ltd. (WST) will supply TF NbSn strands using internal tin route for ITER, and over 6,000 km of NbSn strands have been produced in the past four years. Main performance of NbSn strands, including critical current, n value, wire diameter, Cu/non-Cu ratio, hysteresis loss and RRR are reported and analyzed in this paper.

Li    Zhang    施一公     Liu    Gao Huixian    Du    Liu    Feng Yong    Zhang Pingxiang    Liu Sheng   

IEEE Transactions on Applied Superconductivity

2016

Xia Lin    Duan Xue-Yan    Liang Yao-Yun    Ying Su    Wrighton Katharine H.    Long Jianyin    Hu Min    Davis Candi M.    Wang Jinrong    Brunicardi F. Charles    施一公     陈晔光    孟安明    Feng Xin-Hua   

Cell

2016

The apoptotic protease-activating factor 1 (Apaf-1) controls the onset of many known forms of intrinsic apoptosis in mammals. Apaf-1 exists in normal cells as an autoinhibited monomer. Upon binding to cytochrome c and dATP, Apaf-1 oligomerizes into a heptameric complex known as the apoptosome, which recruits and activates cell-killing caspases. Here we present an atomic structure of an intact mammalian apoptosome at 3.8 Å resolution, determined by single-particle, cryo-electron microscopy (cryo-EM). Structural analysis, together with structure-guided biochemical characterization, uncovered how cytochrome c releases the autoinhibition of Apaf-1 through specific interactions with the WD40 repeats. Structural comparison with autoinhibited Apaf-1 revealed how dATP binding triggers a set of conformational changes that results in the formation of the apoptosome. Together, these results constitute the molecular mechanism of cytochrome c- and dATP-mediated activation of Apaf-1.

Zhou Mengying    Li Yini    Hu Qi    Xiaochen Bai    Huang Weiyun    Chuangye Yan    Sjors Scheres    施一公    

Genes and Development

2015

Multistep heat treatments are required to produce the superconducting NbSn in the International Thermonuclear Experimental Reactor toroidal field coils; however, deviations in the temperature and dwell time during heat treatment of the big conductors are unavoidable, and these could affect the performance of the NbSn strands. To investigate the influence of heat treatment tolerances, both internal-Sn- and bronze-process-type NbSn strands were heat treated with different cycles. For the internal-Sn process strands, the critical current density J increases as the temperature increases from 630°C to 650°C and remains unchanged at 670°C for 100 h. The Sn content in the filament increases with increasing temperature, and the grain sizes significantly increase from an average of 130-202 nm from 630°C to 670°C. For both the internal-Sn process strands and bronze route strands, Jcn seldom changes when the duration at 650°C is increased from 100 to 200 h. Despite these changes, this study shows that NbSn strands are not very sensitive to small heat treatment variations at 650°C, and a variance of ±5°C is acceptable for both types of NbSn strands.

Zhang Ke    Zhang Pingxiang    施一公     Liu    Gao    Jia    Guo    Li    Liu Xianghong    Feng   

IEEE Transactions on Applied Superconductivity

2015

In this study, internal tin process NbSn strands for the International Thermo-nuclear Experimental Reactor are developed in Western Superconducting Technologies. Short cable-in-conduit conductors manufactured with these strands have been qualified. Mass production is accomplished, and all the performances of the strands meet the requirement of ITER project. Besides, more researches on the effect of strand design on critical current density and hysteresis loss for NbSn strands are carried out. It is found that critical current density can be enhanced by reducing filament diameter and increasing Sn content, and hysteresis loss of the strands can be significantly reduced through Cu split adopted in sub-element.

Zhang Ke    Zhang Pingxiang    施一公     Liu Jianwei    Gao    Li Jianfeng    Liu Xianghong    Feng   

Fusion Engineering and Design

2015