Structure of the AAA protein Msp1 reveals mechanism of mislocalized membrane protein extraction.

The AAA protein Msp1 extracts mislocalized tail-anchored membrane proteins and targets them for degradation, thus maintaining proper cell organization. How Msp1 selects its substrates and firmly engages them during the energetically unfavorable extraction process remains a mystery. To address this question, we solved cryo-EM structures of Msp1-substrate complexes at near-atomic resolution. Akin to other AAA proteins, Msp1 forms hexameric spirals that translocate substrates through a central pore. A singular hydrophobic substrate recruitment site is exposed at the spiral's seam, which we propose positions the substrate for entry into the pore. There, a tight web of aromatic amino acids grips the substrate in a sequence-promiscuous, hydrophobic milieu. Elements at the intersubunit interfaces coordinate ATP hydrolysis with the subunits' positions in the spiral. We present a comprehensive model of Msp1's mechanism, which follows general architectural principles established for other AAA proteins yet specializes Msp1 for its unique role in membrane protein extraction

Comparative Analysis of Microbial Community between Mechanized and Traditional Stack Fermentation of Fermented Grains for Fuhexiangxing Baijiu

High-throughput sequencing technology was used to analyze the microbial community of fermented grains for Fuhexiangxing baijiu during mechanized and traditional stack fermentation. The results showed that microbial exchange, succession and enrichment occurred during the fermentation process. In both fermented grains, the microbial communities were composed of four major bacterial genera including Bacillus, Weissella, Acetobacter and Ralstonia, and six major fungal genera including Aspergillus, Lichtheimia, Candida, Pichia, Wickerhamomyces and Saccharomyces. The diversity of bacteria was significantly higher in mechanized than traditional stack fermentation, while the diversity of fungi was significantly lower in traditional than mechanized stack fermentation. Moreover, bacterial diversity was lower on the surface than in the interior of fermented grains, whereas fungal diversity was higher on the surface than in the interior of fermented grains. These results provide a basis for continuous optimization of the mechanized brewing process of Fuhexiangxing baijiu and for improving the quality of base baijiu

COVID-19 in Japan: What could happen in the future? (Recent developments on inverse problems for partial differential equations and their applications)

This paper was finished in February, 2020 and posted in MedRxiv on Feb. 28th, 2020.COVID-19 has been impacting on the whole world critically and constantly Since December 2019. We have independently developed a novel statistical time delay dynamic model on the basis of the distribution models from CCDC. Based only on the numbers of confirmed cases in different regions in China, the model can clearly reveal that the containment of the epidemic highly depends on early and effective isolation. We apply the model on the epidemic in Japan and conclude that there could be a rapid outbreak in Japan if no effective quarantine measures are carried out immediately

Precise Design of Protein Structures

Proteins perform most of biological functions. The ultimate approach to understand protein functions is designing novel protein functions from scratch. The ability to design novel functional proteins would also be revolutionary for biology research, medicine and synthetic biology. Proteins function by placing specific chemical groups at precise 3-dimensional (3D) positions and orientations. Therefore, de novo functional protein design relies on precise control of protein 3D structures. In this thesis, I review the recent advances in de novo protein design (chapter 1). Then I describe two of my research projects that aim to extend the ability of computational methods to design precise protein 3D structures. In the first project (chapter 2), I developed a method termed loop-helix-loop unit combinatorial sampling (LUCS) that systematically samples geometries of protein secondary structures. I applied LUCS to designs de novo protein fold families of two topologies. In the second project (chapter 3), I developed two computational methods termed fragment kinematic closure (FKIC) and loophash kinematic closure (LHKIC) for modeling protein local segments. FKIC predicts protein local segment structures with significantly higher accuracy and efficiency than previous methods. LHKIC designs local segment structures by combining the power of the loophash algorithm and the kinematic closure algorithm. I expect these new methods can bring the ideal of designing arbitrary protein functions closer to reach

Precise Design of Protein Structures

Proteins perform most of biological functions. The ultimate approach to understand protein functions is designing novel protein functions from scratch. The ability to design novel functional proteins would also be revolutionary for biology research, medicine and synthetic biology. Proteins function by placing specific chemical groups at precise 3-dimensional (3D) positions and orientations. Therefore, de novo functional protein design relies on precise control of protein 3D structures. In this thesis, I review the recent advances in de novo protein design (chapter 1). Then I describe two of my research projects that aim to extend the ability of computational methods to design precise protein 3D structures. In the first project (chapter 2), I developed a method termed loop-helix-loop unit combinatorial sampling (LUCS) that systematically samples geometries of protein secondary structures. I applied LUCS to designs de novo protein fold families of two topologies. In the second project (chapter 3), I developed two computational methods termed fragment kinematic closure (FKIC) and loophash kinematic closure (LHKIC) for modeling protein local segments. FKIC predicts protein local segment structures with significantly higher accuracy and efficiency than previous methods. LHKIC designs local segment structures by combining the power of the loophash algorithm and the kinematic closure algorithm. I expect these new methods can bring the ideal of designing arbitrary protein functions closer to reach

Structure of the AAA protein Msp1 reveals mechanism of mislocalized membrane protein extraction.

The AAA protein Msp1 extracts mislocalized tail-anchored membrane proteins and targets them for degradation, thus maintaining proper cell organization. How Msp1 selects its substrates and firmly engages them during the energetically unfavorable extraction process remains a mystery. To address this question, we solved cryo-EM structures of Msp1-substrate complexes at near-atomic resolution. Akin to other AAA proteins, Msp1 forms hexameric spirals that translocate substrates through a central pore. A singular hydrophobic substrate recruitment site is exposed at the spiral's seam, which we propose positions the substrate for entry into the pore. There, a tight web of aromatic amino acids grips the substrate in a sequence-promiscuous, hydrophobic milieu. Elements at the intersubunit interfaces coordinate ATP hydrolysis with the subunits' positions in the spiral. We present a comprehensive model of Msp1's mechanism, which follows general architectural principles established for other AAA proteins yet specializes Msp1 for its unique role in membrane protein extraction

Evaluation of Bacterial Diversity and Quality Features of Traditional Sichuan Bacon from Different Geographical Region

Sichuan bacon is one of the most popular types of Chinese bacon in the domestic market. High-throughput sequencing was used to characterize the bacterial diversity of 39 Sichuan bacon samples collected from 3 geographical regions. The results showed that the bacterial diversity of Sichuan bacon in different regions demonstrated certain specificity as well as similarity, and the shared OTUs were close to 81% of the total number in the basin group, mountain group, and plateau group. At the genus level, Staphylococcus is the most dominant genus among the three groups, covering 26.7%, 20.6%, and 22.7%, respectively. Beta diversity shows significant differences in bacterial compositions in different geographic regions, especially for Pseudomonas, Brochothrix, Lactobacillus, Lactococcus, and Enterococcus. Meanwhile, some physicochemical characteristics were analyzed, and a significant difference (p < 0.05) among the three regions was shown in the Aw, pH, and nitrite content, which were significantly correlated with undesired bacteria. This study provides insights into the understanding of the role of bacterial communities in the microbial safety and quality improvement of Sichuan bacon