Progress | Human eyes prevent ultraviolet light damage from the molecular mechanism of cataracts

On May 26, 2022, Biophysical Journal Magazine reported online the Institute of Physics of the Chinese Academy of Sciences/Beijing Condensing Physics National Research Center Weng Yuxiang Research Team (SM6 group) entitled "α lens protein players under thermal induction under thermal induction Molecular partner function inhibits γD crystal protein research under ultraviolet irrades that occur in the measured molecular mechanism (The Mechanism for thermal-Erianced Chaperone-Like Activity of α-Crystallinst Uv Irradiation-induced. This work is combined with the research group of Bao Yongzhen, the People's Hospital of Peking University, a combination of high-intensity projects at the Shenzhen Bay Laboratory Quantum Biology, and Applying the Prosperity of the Light Plastic Spectrum (LC-MS), the Fourier transform With the pulse heating (T-JUMP) nano-seconds time to distinguish between the middle infrared transient spectrum and other means, it reveals that the heat-induction of the alpha crystal oligopoly part of the alpha crystal oligraphy is dissolved in the aqueous solution. The γD lens molecular molecules of ultraviolet radiation damage are combined to form αγ heterogeneous diocol. This heteroglist can spontaneously assembled on the alpha crystal oligoscopy that is partially unlied under the physiological temperature conditions, thereby avoiding the aggregation of ultraviolet radon injury γD crystals. Strong scattering effect is one of the causes of cataract. This proposes a molecular mechanism for alpha lens protein to inhibit ultraviolet radon injury γD lens protein, achieve its high -efficiency molecular partner activity, and prevent ultraviolet radiation from causing cataract. Doctor of the Institute of Physics of the Chinese Academy of Sciences (post -doctoral postgraduate of Shenzhen Graduate School of Peking University, a visiting scholar of Shenzhen Bay Lab) Li Hao is the first author of the paper, and Weng Yuxiang and Bao Yongzhen are contacts.

Cataract is the world's primary blind eye disease, and the age correlation cataract is the most important type. With the intensification of aging processes and the huge population base in my country, the number of cataract patients has a huge burden on society and families, and it also seriously affects the quality of life of elderly groups. The Bao Yongzhen research group of Peking University People's Hospital from 2003 to 2005 was surveyed by senior cataracts in the rural areas of western China. He and Guangxi (39.4%) are far higher than the cataract disease rate of cataracts in the eastern region. Due to the high altitude and low latitudes of the southwestern region, the relatively high ultraviolet radiation is the main reason for this result. UV radiation is usually considered to be the main risk factors in the process of natural aging that causes elderly cataracts, and epidemiological studies have shown this view.

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The crystal is the main refractive medium of the eye, and the transcarity of the lens is cataract (Figure 1). The most important component of crystal is crystal protein. Crystal proteins contain three families of α, β and γ, of which α-lens protein accounts for 50%. α-crystal protein includes 2 subtypes: αA (173 amino acid residues) and αb (175 amino acid residue). In normal crystals, the crystal protein molecules are arranged in an orderly manner to maintain the high -pass light of the lens. Factors such as ultraviolet rays, high temperature, ozone, etc. can cause influence of protein, causing a single state such as γ lens protein to gather. Once the protein gathering collective formation of starch -like precipitation, the order of the crystal structure will be destroyed, which will cause eye disease diseases such as cataracts. α crystal proteins usually exist in the form of oligoplasty in vitro with 30-50 monomers, and can still maintain transparency at higher physiological temperature conditions. The molecular structure of the binding surface between the monomers is shown in Figure 2A, B.白 Crystal protein, as an important transistor structure, is also a small hot shock protein (SHSP). It has the activity of molecular partners and effectively suppresss other lens protein after injury. Although the molecular partner activity of α lens protein was discovered 20 years ago, the molecular mechanism involved has not been revealed. The difficulty is the dynamic balance composed of alpha crystals under room temperature conditions. The X-ray crystal structure and complete freezer electron microscope structure that cannot be obtained at present.

As a structural protein of the crystal, the γD lens protein exists in the core of the crystal and has a high content in the form of a single body. The thermodynamic stability of its structure depends on the four conservatives (TRP) residues (see Figure 2C). Under normal circumstances, when ultraviolet rays reach the crystal body, the color of the color can be transformed through rapid energy transfer to the thermal energy to prevent the protein molecule from occurring with photochemical reactions. However, continuous ultraviolet radiation will still lead to photochemical cracking of the peptide chain, and this light damage process is also related to active oxygen.

Figure 2. A schematic diagram of α lens protein and γD lens protein structure. (A) and (B) are schematic diagrams of frozen electron microscopy structures of αA and αB crystal protein di agents in the literature. In the figure, the hydrogen bonding of the di -polymer interface is marked with a dotted line. (B) The key highlights the hydrogen bonds formed by the R (ARG) 107 and D (ASP) 80 between the αB crystal protein adjacent to the sub -jam. (C) Diagram of the γD lens protein monomer structure reported by the literature. The picture marked 4 conservative color picots W (TRP) and enlarged the protein structure near W156-A158. Among them, the shortest distance of the 吲哚 ring distance of the A158 amino nitrogen atom is 4.14å, and the W156 free base can be possible at this distance. Energy transmission with the peptide chain of A158. This study first confirmed that the α lens protein has a curbing effect on the γD lens protein aggregation of ultraviolet radiation (325nm), and this role increases with the increase in temperature. Directly leads to turbidity of γD lens protein and eventually forms a precipitation. Subsequently, the combination of hydrophobic fluorescent probe confirmed that the binding surface of α lens protein and γD lens protein occurred on the hydrophobic surface formed by the alpha lens protein vertical heating, and through the chromatography method, α lens protein and ultraviolet radiation were injured. The crystal mixture is separated from alpha γ crystal heterogeneity, and further uses the atomic force microscope (AFM) and the dynamic light scattering (DLS) method to verify the complex (volume is greater than the same conditions under the same conditions under the same conditions of α -crystalline body binding of ultraviolet injury (volume is greater than the same conditions Simple α crystal). At the same time, the chromatography-mass spectrometry method analysis shows that ultraviolet radiation can cause γD lens protein under the protection of alpha lens protein to break the covalent key to break the covalent key at the C-end ALA158 site, and drop a section of peptide chain containing 15 amino acids.

By warming the ftir and T-JUMP nano-seconds time to distinguish between the fourth-level structure of α lens protein (the structure of the monomer to be assembled into an oligopoly) and the second-level structure (β sheet, β-curved, β-curved Study for discount, irregular curls, etc.). Based on the infrared spectrum during the warming, the experiment found that the α lens protein vermicullet is solved from the monomer molecule under the heat induction. The method confirmed that the 1604 CM-1 infrared absorption peak came from the inter-hydrogen bond between the diocyst binding interface, and used it as a spectral indicator for alpha lens thermal induction to be aggregated into a monomer process. For the infrared spectrum, through the Single Value Decomposition method, the medium -infrared spectrum of α lens protein is divided into three components with different hydrophobicity in different temperature intervals: Solid molecules and alpha lens protein from the solution and the exposed hydrophobic shell layer exposed after dissolving the α lens protein (Figure 3). This model is consistent with the three -layer nuclear shell layer models distributed by the biologist with a gradient distribution: the kernel is the most hydrophobic, the second level, and the outermost layer of the most hydrophilic.

Figure 3. In the second -order derivatives of α crystal protein, the infrared spectrum and the corresponding hot -drop fixed curve in the two different components.

(A) α crystal protein in the two-order guide in the three components of the three components in the temperature of 25-64 ℃. Including the inner layer of the most hydrophobic group (Component 1), the monomer (Component 2) from the solution, and the most hydrophilic component 3 in the outer layer (Component 3). (B) The number of α crystal protein components in different temperatures.

Based on this, the molecular mechanism of α lens protein shown in FIG. 4B inhibit UV light -induced γ lens protein aggregation: The γD lens protein with ultraviolet injury and the alpha lens monomer protein combined with the α γ complex. The complex is re -combined with the partially unbuttoned alpha crystal protein polymer, which prevent the protein precipitation caused by the gamma crystal protein. The α -crystal eggs are given to the molecular partner function through thermal inducement to the monomer to achieve the protection mechanism of ultraviolet -induced white internal barriers. However, α crystal damage to ultraviolet radiation γD crystal protection is based on the cost of cutting the γD crystal protein C -end short peptide (see Figure 4A).

Figure 4. The diagram of the peptide chain cracking pathway and the alpha lens protein protecting the substrate γD lens protein under thermal induction. (A) Ultraviolet sphere, in the γD lens protein, the peptide chain cracking pathway caused by the color of the chromine (TRP).

(B) Diagram of the mechanism of alpha crystal protein molecular partners under thermal induction. The temperature interval of this mechanism is 25-43 ° C. The process involves the combination of monomer detachment (KD), α lens and D crystal body monomers (KB) and αγ complexes to the α lens (KBϒ) (KBϒ) (KBϒ)

Weng Yuxiang's research team of the Soft Material Physics Laboratory of the Institute of Physics of the Chinese Academy of Sciences has developed a pulse warming and nano time to distinguish the infrared spectrum technology. Combine the dynamic process of hydrogen bonding of interface molecular intermorses and other secondary structure changes. (Biophys. J. 2007, 93, 2756-2766, Rev. SCI. Instr. 86, 053105,2015). In the past work, the molecular mechanism of bacterial reduction of sulfur sulfur differential enzyme (DSBC) diocytes participating in the abnormal phenomenon of the oxidation pathway (BIOPHYSICAL JIURNAL, 97, 2811–2819, 2009) Bacteria DEGP thermal shock protein realizes the process of solving dynamics from hexagon to trimers through the "Protein Quake" mode, clarifying the key role of environmental temperature on activation of degp enzymatic activity (SCI. REP. 4 , 4834-4840,2014); revealed the high-plant light system II main lighting antenna protein composite (Light Harvesting Complex II (LHCII) trimer, as a protein molecular machine, how to achieve high-efficiency light capture and light protection function rooms Reverse switching mechanism (Science China-Chemistry 63, 1121-1133, 2020). The study was supported by the National Natural Science Foundation of China (21433014, 11721404, and 21173012 and the Chinese Academy of Sciences (QYZDJ-SSW-SYS017 and YJKYYQ20170046).

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