Chinese Journal of Nature

Molecular insights into mechanisms of cohesin in genome maintenance

SHI Zhubing, BAI Xiaochen, YU Hongtao

2021, 43(1): 1-8. doi:10.3969/j.issn.0253-9608.2020.00.003

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Cohesin is a key player in genome maintenance. During mitosis, cohesin mediates sister chromatid cohesion and plays an essential role in chromosome segregation. Recent research discovered that cohesin also organizes the 3D genome during interphase and is crucial for the formation of chromatin loops and topologically associating domains (TADs) in mammalian cells. The latest biophysical and structural studies have provided insights into the underlying mechanisms by which cohesin is loaded onto DNA and extrudes DNA loops.

Advances in device physics of nanomotors

ZHU Fangyan, CHANG Tienchong

2021, 43(1): 9-17. doi:10.3969/j.issn.0253-9608.2021.01.002

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As one of nanoscale energy conversion devices, nanomotors can realize directional motion by transforming other forms of energy into mechanical energy. This article presents a brief review on recent advances in device physics of nanomotors, with a concise discussion about their limitations in practical applications and a preliminary prospect of the field.

Structural and signaling mechanism of chemokine receptors

LIU Kaiwen, LIU Zhijie, HUA Tian

2021, 43(1): 18-24. doi:10.3969/j.issn.0253-9608.2021.01.003

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Chemokine and chemokine receptor play important roles in cell migration, proliferation and resisting invasion, thus closely related with multiple fundamental biological processes and disease development in immune environment, such as inflammation and cancer. There are more than 20 different chemokine receptors and nearly 50 chemokines in human body. One chemokine can bind multiple receptors and vice versa. Their interaction forms a complex chemokine regulatory network. Analysis of the three-dimensional structures of chemokines and their receptors will further improve our understanding of the activation mechanism and pharmacological functions of the chemokine receptor family. Here, we briefly review the solved structure of chemokine receptors bound with chemokine ligands or their analogs, and analyze the structure and activation mechanism of chemokine receptors, and indicate the importance of the anticancer drug development of chemokine receptor family.

Structural studies of human cannabinoid receptors

SHEN Ling, HUA Tian, LIU Zhijie

2021, 43(1): 25-31. doi:10.3969/j.issn.0253-9608.2021.01.004

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Marijuana from Cannabis sativa L. has been used for both therapeutic and recreational purpose for many centuries. Δ9 - tetrahydrocannabinol (Δ9 -THC), the main psychoactive constituent of marijuana, was discovered and isolated in 1964. In the early 1990s, the endocannabinoid system was identified in mammalian species. The cannabinoids from marijuana and endocannabinoids exert their effects mainly through the cannabinoid receptors CB1 and CB2, which belong to the G protein-coupled receptors (GPCRs). CB1 is highly expressed in the central nervous system, while CB2 is widely distributed in the immune system. CB1 and CB2 can regulate a variety of central and peripheral physiological processes and are very important drug targets for treating diverse diseases. Here, we briefly summarized the history of cannabinoids and the progress in the structural and functional studies of CB1 and CB2, and discussed their therapeutic potentials in learning, mood, obesity, pain and inflammation.

Developing the affinity mass spectrometry technology for the discovery of chemical ligands and drug leads towards GPCR targets

ZHANG Bingjie, SHUI Wenqing

2021, 43(1): 32-38. doi:10.3969/j.issn.0253-9608.2021.01.005

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Affinity mass spectrometry (affinity MS) based on the detection of protein target-ligand interaction is a powerful technology complementary to conventional high-throughput screening (HTS) assays and has been successfully incorporated into the early-phase lead discovery pipeline. Owing to the special biochemical properties of G protein-coupled receptors (GPCRs), tremendous technical challenges are posed to affinity MS-based ligand screening for GPCR targets. Here we briefly summarize the principle and features of the affinity MS technique adapted to GPCR ligand screening, and review the recent progress in screening both large-scale compound libraries and natural herb extracts with affinity MS for discovery of unreported GPCR ligands and modulators.

Advances in AAV-mediated gene therapy for hearing loss

KE Junzi, TAN Fangzhi, ZHONG Guisheng

2021, 43(1): 39-44. doi:10.3969/j.issn.0253-9608.2021.01.006

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Hearing loss is one of the common sensory disorders, and there is no non-device means to restore hearing. In recent years, gene therapy for hearing diseases has gradually moved to the forefront of scientific research and clinical practice. Adeno-associated virus（AAV）is the most commonly used gene therapy vector and plays an important role in the gene therapy of hearing diseases. In this paper, the structure and type of natural AAV were briefly reviewed, and the possibility of AAV-mediated gene therapy for hearing loss was discussed with Anc80L65, AAV2.7m8 and AAV-ie as examples, and the future progress of AAV-mediated gene therapy for hearing loss was also discussed.

Common activation mechanism of GPCR

ZHOU Qingtong, DAI Zhizhuo, ZHAO Suwen

2021, 43(1): 45-52. doi:10.3969/j.issn.0253-9608.2021.01.007

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G protein-coupled receptor (GPCR) family is the largest and most diverse group of membrane receptors in eukaryotes. By mediating a wide variety of physiological functions, GPCRs are important drug targets with around 500 marketed drugs. The breakthrough of GPCR structural studies leads to the determinations of over 400 structures, which highlights the diversified ligandbinding modes and signal transduction mechanisms across GPCRs. In recent years, a common activation mechanism of class A GPCRs has been discovered, by using residue-residue contact score (RRCS) that can quantitatively describes the rearrangements of residue contacts upon receptor activation. Here, we briefly summarize the approaches utilized in GPCR activation mechanism, and also discuss the significance of understanding GPCR activation mechanism on functional studies and drug discovery.

Large activation entropy is a key factor to trigger the memory effect of amorphous alloys

SONG Lijian, XU Wei, HUO Juntao, WANG Junqiang

2021, 43(1): 53-60. doi:10.3969/j.issn.0253-9608.2021.01.008

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The enthalpy and volume of materials in metastable states, such as amorphous materials and glasses, always decay simultaneously through an energy-driven process called ‘‘ageing’’. This is one of the intrinsic characteristics of non-equilibrium systems. As opposed to the common monotonic relaxation process of ageing, the memory effect describes an isothermal annealing experiment, in which the enthalpy/volume of a pre-annealed glass first increases before finally decreasing towards equilibrium. If the system reaches its equilibrium state, its memory to the past states will vanish thoroughly. For the past half century, phenomenological models such as the Tool-Narayanaswamy-Moynihan (TNM) model have been used to describe the memory effect, but its underlying physical mechanismsare still not clear. In this paper, the relaxation kinetics in single and two-temperature annealing processes was studied. According to our research, there was a transition from β relaxation to α relaxation in amorphous alloys during isothermal annealing. We further discovered that a large activation entropy (S*) is the key factor to trigger on the memory effect. These results open a gate for understanding the physical origin of non-equilibrium systems and precisely modifying their properties.

Carbon dioxide conversion by solar energy

WANG Feng, ZHOU Hualan, ZHANG Jianguo

2021, 43(1): 61-70. doi:10.3969/j.issn.0253-9608.2021.01.009

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