Shengli Zhang

Structural basis of transfer between lipoproteins by cholesteryl ester transfer protein

Human cholesteryl ester transfer protein (CETP) mediates the net transfer of cholesteryl ester mass from atheroprotective high-density lipoproteins to atherogenic low-density lipoproteins by an unknown mechanism. Delineating this mechanism would be an important step toward the rational design of new CETP inhibitors for treating cardiovascular diseases. Using EM, single-particle image processing and molecular dynamics simulation, we discovered that CETP bridges a ternary complex with its N-terminal β-barrel domain penetrating into high-density lipoproteins and its C-terminal domain interacting with low-density lipoprotein or very-low-density lipoprotein. In our mechanistic model, the CETP lipoprotein-interacting regions, which are highly mobile, form pores that connect to a hydrophobic central cavity, thereby forming a tunnel for transfer of neutral lipids from donor to acceptor lipoproteins. These new insights into CETP transfer provide a molecular basis for analyzing mechanisms for CETP inhibition.

Morphology and structure of lipoproteins revealed by an optimized negative-staining protocol of electron microscopy

Plasma lipoprotein levels are predictors of risk for coronary artery disease. Lipoprotein structure-function relationships provide important clues that help identify the role of lipoproteins in cardiovascular disease. The compositional and conformational heterogeneity of lipoproteins are major barriers to the identification of their structures, as discovered using traditional approaches. Although electron microscopy (EM) is an alternative approach, conventional negative staining (NS) produces rouleau artifacts. In a previous study of apolipoprotein (apo)E4-containing reconstituted HDL (rHDL) particles, we optimized the NS method in a way that eliminated rouleaux. Here we report that phosphotungstic acid at high buffer salt concentrations plays a key role in rouleau formation. We also validate our protocol for analyzing the major plasma lipoprotein classes HDL, LDL, IDL, and VLDL, as well as homogeneously prepared apoA-I-containing rHDL. High-contrast EM images revealed morphology and detailed structures of lipoproteins, especially apoA-I-containing rHDL, that are amenable to three-dimensional reconstruction by single-particle analysis and electron tomography.

Could Borophene Be Used as a Promising Anode Material for High-Performance Lithium Ion Battery?

The rapid development of electronic products has inspired scientists to design and explore novel electrode materials with an ultrahigh rate of charging/discharging capability, such as two-dimensional (2-D) nanostructures of graphene and MoS2. In this study, another 2-D nanosheet, that is a borophene layer, has been predicted to be utilized as a promising anode material for high-performance Li ion battery based on density functional theory calculations. Our study has revealed that Li atom can combine strongly with borophene surface strongly and easily, and exist as a pure Li(+) state. A rather small energy barrier (0.007 eV) of Li diffusion leads to an ultrahigh diffusivity along an uncorrugated direction of borophene, which is estimated to be 10(4) (10(5)) times faster than that on MoS2 (graphene) at room temperature. A high Li storage capacity of 1239 mA·h/g can be achieved when Li content reaches 0.5. A low average operating voltage of 0.466 V and metallic properties result in that the borophene can be used as a possible anode material. Moreover, the properties of Li adsorption and diffusion on the borophene affected by Ag (111) substrate have been studied. It has been found that the influence of Ag (111) substrate is very weak. Li atom can still bind on the borophene with a strong binding energy of -2.648 eV. A small energy barrier of 0.033 eV can be retained for Li diffusion along the uncorrugated direction, which can give rise to a high Li diffusivity. Besides, the performances of borophene-based Na ion battery have been explored. Our results suggest that an extremely high rate capability could be expected in borophene-based Li ion battery.

Optimal helicity of single-walled carbon nanotube

Abstract We find that the optimal helical angle of the SWNT varies with its length for the fixed number of carbon hexagons along the tubular perimeter. The longer the tube is, the larger the helical angle is, in which the helical angle is defined with respect to the zigzag configuration. The armchair is the optimal helical configuration of the SWNT when its length is long enough.

An optimized negative-staining protocol of electron microscopy for apoE4•POPC lipoprotein

Apolipoprotein E (apoE), one of the major protein components of lipoproteins in the peripheral and central nervous systems, regulates cholesterol metabolism through its interaction with members of the low density lipoprotein receptor family. One key to understanding apoE function is determining the structure of lipid-bound forms of apoE. Negative-staining (NS) electron microscopy (EM) is an easy and rapid approach for studying the structure and morphology of lipid-bound forms of apoE. However, an artifact of using the conventional NS protocol is that the apoE•phospholipid particles form rouleaux. In this study, we used cryo-electron microscopy (cryo-EM) to examine apoE4•palmitoyl-oleoylphosphatidylcholine (POPC) particles in a frozen-hydrated native state. By comparing the particle sizes and shapes produced by different NS protocols to those produced by cryo-EM, we propose an optimized protocol to examine apoE4•POPC particles. Statistical analysis demonstrated that the particle sizes differ by less than 5% between the optimized protocol and the cryo-EM method, with similar shapes. The high contrast and fine detail of particle images produced using this optimized protocol lend themselves to the structural study of lipid-bound forms of apoE.

3D Structural Fluctuation of IgG1 Antibody Revealed by Individual Particle Electron Tomography

Commonly used methods for determining protein structure, including X-ray crystallography and single-particle reconstruction, often provide a single and unique three-dimensional (3D) structure. However, in these methods, the protein dynamics and flexibility/fluctuation remain mostly unknown. Here, we utilized advances in electron tomography (ET) to study the antibody flexibility and fluctuation through structural determination of individual antibody particles rather than averaging multiple antibody particles together. Through individual-particle electron tomography (IPET) 3D reconstruction from negatively-stained ET images, we obtained 120 ab-initio 3D density maps at an intermediate resolution (~1–3 nm) from 120 individual IgG1 antibody particles. Using these maps as a constraint, we derived 120 conformations of the antibody via structural flexible docking of the crystal structure to these maps by targeted molecular dynamics simulations. Statistical analysis of the various conformations disclosed the antibody 3D conformational flexibility through the distribution of its domain distances and orientations. This blueprint approach, if extended to other flexible proteins, may serve as a useful methodology towards understanding protein dynamics and functions.

Structural features of cholesteryl ester transfer protein: A molecular dynamics simulation study

Cholesteryl ester transfer protein (CETP) mediates the net transfer of cholesteryl esters (CEs) from atheroprotective high‐density lipoproteins (HDLs) to atherogenic low‐density lipoproteins (LDLs) or very‐low‐density lipoproteins (VLDLs). Inhibition of CETP raises HDL cholesterol (good cholesterol) levels and reduces LDL cholesterol (bad cholesterol) levels, making it a promising drug target for the prevention and treatment of coronary heart disease. Although the crystal structure of CETP has been determined, the molecular mechanism mediating CEs transfer is still unknown, even the structural features of CETP in a physiological environment remain elusive. We performed molecular dynamics simulations to explore the structural features of CETP in an aqueous solution. Results show that the distal portion flexibility of N‐terminal β‐barrel domain is considerably greater in solution than in crystal; conversely, the flexibility of helix X is slightly less. During the simulations the distal end of C‐terminal β‐barrel domain expanded while the hydrophilic surface increasing more than the hydrophobic surface. In addition, a new surface pore was generated in this domain. This surface pore and all cavities in CETP are stable. These results suggest that the formation of a continuous tunnel within CETP by connecting cavities is permitted in solution. Proteins 2013.

The modulation of the de Haas–van Alphen effect in graphene by electric field

This paper explores the de Haas-van Alphen effect (dHvA) of graphene in the presence of an in-plane uniform electric field. Three major findings are yielded. First of all, the electric field is found to modulate the de Haas-van Alphen magnetization and magnetic susceptibility through the dimensionless parameter (β = E/(v(F)B). As the parameter β increases, the values of magnetization and magnetic susceptibility increase to positive infinity or decrease to negative infinity at the exotic point β(c) = 1. Furthermore, the dHvA oscillation amplitude rises abruptly to infinity for zero temperature at β(c) = 1, but eventually collapses at a finite temperature, thereby leading to the de Haas-van Alphen effect vanishing. In addition, the magnetic susceptibility depends on the electric and magnetic fields, suggesting that graphene should be a non-linear magnetic medium in the presence of an external field. These results, which are different from those obtained in the standard non-relativistic 2D electron gas, are attributed to the anomalous Landau level spectrum of graphene.

Interconversion between three overstretched DNA structures

Double-stranded DNA can exist in multiple structures, including three recently identified overstretched structures (peeled ssDNA, DNA bubble, and S-DNA) for torsion-unconstrained DNA under large tension. Here, we report systematic studies of interconversion between these overstretched DNA structures induced by changing NaCl concentration at constant force. At forces above 70 pN where DNA exists in one of the overstretched states, direct interconversions between S-DNA and DNA bubble for the end-closed DNA construct, as well as interconversions between S-DNA and peeled ssDNA for the end-opened DNA construct, were observed to involve stepwise extension changes. Interestingly, compared to other conversions, the conversion from peeled ssDNA to S-DNA has ultraslow kinetics, which can be explained by formation of secondary hairpin structures on a relaxed strand of peeled ssDNA. Our findings provide important insights into the structures of torsion-unconstrained DNA under large force.

Graphdiyne as a promising material for detecting amino acids

The adsorption of glycine, glutamic acid, histidine and phenylalanine on single-layer graphdiyne/ graphene is investigated by ab initio calculations. The results show that for each amino acid molecule, the adsorption energy on graphdiyne is larger than the adsorption energy on graphene and dispersion interactions predominate in the adsorption. Molecular dynamics simulations reveal that at room temperature the amino acid molecules keep migrating and rotating on graphdiyne surface and induce fluctuation in graphdiyne bandgap. Additionally, the photon absorption spectra of graphdiyne-amino-acid systems are investigated. We uncover that the presence of amino acid molecules makes the photon absorption peaks of graphdiyne significantly depressed and shifted. Finally, quantum electronic transport properties of graphdiyne-amino-acid systems are compared with the transport properties of pure graphdiyne. We reveal that the amino acid molecules induce distinct changes in the electronic conductivity of graphdiyne. The results in this paper reveal that graphdiyne is a promising two-dimensional material for sensitively detecting amino acids and may potentially be used in biosensors.