CD4-binding obstacles in conformational transitions and allosteric communications of HIV gp120.

As the only exposed viral protein at the membrane surface of HIV, envelope glycoprotein gp120 is responsible for recognizing host cells and mediating virus-cell membrane fusion. Available structures of gp120 indicate that it exhibits two distinct conformational states, called closed and open states. Although experimental data demonstrates that CD4 binding stabilizes open state of gp120, detailed structural dynamics and kinetics of gp120 during this process remain elusive. Here, two open-state gp120 simulation systems, one without any ligands (ligand-free) and the other complexed with CD4 (CD4-bound), were subjected to microsecond-scale molecular dynamics simulations following the conformational transitions and allosteric pathways of gp120 evaluated by using the Markov state model and a network-based method, respectively. Our results provide an atomic-resolution description of gp120 conformational transitions, suggesting that gp120 is intrinsically dynamic from the open state to closed state, whereas CD4 binding blocks these transitions. Consistent with experimental structures, five metastable conformations with different orientations of the V1/V2 region and V3 loop have been extracted. The binding of CD4 significantly enhances allosteric communications from the CD4-binding site to V3 loop and ß20-21 hairpin, resulting in high-affinity interactions with coreceptors and activation of the conformational transitions switcher, respectively. This study will facilitate the structural understanding of the CD4-binding effects on conformational transitions and allosteric pathways of gp120.

[Analysis of heavy metals distribution characteristics and pollution assessment in agricultural region soils of Huaihe basin].

By means of field sampling and laboratory analysis, the content distribution characteristics of Cd, Cr, Cu, Ni, Pb and Zn in agricultural region soils of Huaihe basin in Anhui province were analyzed. Assessment of heavy metal pollutions was conducted using enrichment factor, geoaccumulation index and potential ecological risk index. The results showed that the average mass fraction of Cd and Cu was 0.113 5 and 22.09 mg x kg(-1) respectively in the study area soil, which were above the background values 0.097 and 20.4 mg x kg(-1) in Anhui Province. The average mass fraction of other four heavy metals did not exceed the average values of Anhui Province. The results of the evaluations from geoaccumulation index and ecological risk assessment discovered that Cd is the strongest pollution metal among six heavy metals in the study area soil. For some samples of the study soil, Cd was slight risk for the ecosystem. The ecosystem risks caused by the other five heavy metals were not obviously for the sampling points. The entire study area soils were mid integrated potential ecological risk.