Mechanistic and Structural Insights on the IL-15 System through Molecular Dynamics Simulations.
Molecules
; 24(18)2019 Sep 06.
Article
in En
| MEDLINE
| ID: mdl-31500206
ABSTRACT
Interleukin 15 (IL-15), a four-helix bundle cytokine, is involved in a plethora of different cellular functions and, particularly, plays a key role in the development and activation of immune responses. IL-15 forms receptor complexes by binding with IL-2Rß- and common γ(γc)-signaling subunits, which are shared with other members of the cytokines family (IL-2 for IL-2Rß- and all other γc- cytokines for γc). The specificity of IL-15 is brought by the non-signaling α-subunit, IL-15Rα. Here we present the results of molecular dynamics simulations carried out on four relevant forms of IL-15 its monomer, IL-15 interacting individually with IL-15Rα (IL-15/IL-15Rα), with IL-2Rß/γc subunits (IL-15/IL-2Rß/γc) or with its three receptors simultaneously (IL-15/IL-15Rα/IL-2Rß/γc). Through the analyses of the various trajectories, new insights on the structural features of the interfaces are highlighted, according to the considered form. The comparison of the results with the experimental data, available from X-ray crystallography, allows, in particular, the rationalization of the importance of IL-15 key residues (e.g. Asp8, Lys10, Glu64). Furthermore, the pivotal role of water molecules in the stabilization of the various protein-protein interfaces and their H-bonds networks are underlined for each of the considered complexes.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Interleukin-2
/
Interleukin-15
/
Multiprotein Complexes
/
Interleukin-2 Receptor beta Subunit
Limits:
Humans
Language:
En
Journal:
Molecules
Journal subject:
BIOLOGIA
Year:
2019
Document type:
Article
Affiliation country:
France