Name
Title | ||
|---|---|---|
Relationships between Th1 or Th2 iNKT cell activity and structures of CD1d-antigen complexes: meta-analysis of CD1d-glycolipids dynamics simulations. |
Abstract | ||
|---|---|---|
A number of potentially bioactive molecules can be found in nature. In particular, marine organisms are a valuable source of bioactive compounds. The activity of an alpha-galactosylceramide was first discovered in 1993 via screening of a Japanese marine sponge (Agelas mauritanius). Very rapidly, a synthetic glycololipid analogue of this natural molecule was discovered, called KRN7000. Associated with the CD1d protein, this a-galactosylceramide 1 (KRN7000) interacts with the T-cell antigen receptor to form a ternary complex that yields T helper (Th) 1 and Th2 responses with opposing effects. In our work, we carried out molecular dynamics simulations (11.5 mu s in total) involving eight different ligands (conducted in triplicate) in an effort to find out correlation at the molecular level, if any, between chemical modulation of 1 and the orientation of the known biological response, Th1 or Th2. Comparative investigations of human versus mouse and Th1 versus Th2 data have been carried out. A large set of analysis tools was employed including free energy landscapes. One major result is the identification of a specific conformational state of the sugar polar head, which could be correlated, in the present study, to the biological Th2 biased response. These theoretical tools provide a structural basis for predicting the very different dynamical behaviors of a-glycosphingolipids in CD1d and might aid in the future design of new analogues of 1. |
Year | DOI | Venue |
|---|---|---|
2014 | 10.1371/journal.pcbi.1003902 | PLOS COMPUTATIONAL BIOLOGY |
Keywords | Field | DocType |
glycolipids,thermodynamics,molecular dynamics simulation,natural killer t cells | Ternary complex,Antigen,Biology,Molecule,Ligand,Biochemistry,Agelas,Natural killer T cell,Molecular dynamics,Computational biology,Genetics,CD1D | Journal |
Volume | Issue | ISSN |
10 | 11 | 1553-734X |
Citations | PageRank | References |
0 | 0.34 | 5 |
Authors | ||
5 | ||
Name | Order | Citations | PageRank |
|---|---|---|---|
| Xavier Laurent | 1 | 0 | 0.34 |
| Nicolas Renault | 2 | 0 | 0.34 |
| Amaury Farce | 3 | 0 | 0.34 |
| Philippe Chavatte | 4 | 12 | 1.51 |
| Eric Henon | 5 | 0 | 1.69 |