MOLECULAR FEATURES OF THE INTEGRIN RECEPTOR AND ITS INTERACTION WITH THE FMDV, AN IN SILICO STUDY

MARRERO, R.; GISMONDI MI; KöNIG G

Bangkok

Congreso; 2019 Meeting of the Global Foot-and-mouth Disease Research Alliance; 2019

GFRA

Foot and Mouth Disease is an agro-economic relevant threat caused by a picornavirus (FMDV) which affects wild and domestic cloven-hoofed animals. At a molecular level, the viral entrance takes place due to host-pathogen interactions, mainly between a FMDV capsid motif (aminoacidic triplet RGD) and cell adhesion molecules, integrins (IT). This landscape is further complex indeed; FMDV not only displays a mere integrin recognition motif at their capsidsurface, but evolved its RGD aminoacidic surroundings for a high affinity to a specific áVâ6 IT receptor, highly expressed in nasopharynx tissues which are the primary infection site. Our aim has been to study the amino acid usage at the áVâ6 IT that determines physicochemical features of great affinity for the FMDV surface at the RGD motif and its context. The recent resolution of the quasi-atomic structure of the human áVâ6 integrin, in complex with an RGD peptide, has paved an avenue for diverse structural studies. Herein, we take advantage of this work of reference and computationally explored the full áVâ6 amino acidic sequence space at the interaction interface with RGD peptide. Our results were of great concordance with previous experimental reports and further points out some novel features ofpotential relevance for such interaction phenomenon. Next, we move up to the bovine host and in silico modeled several bovine áVâx ITs in complex with an RGD FMDV peptide, and fully studied (by single mutants) the preferred aminoacidic substitutions at the interaction interface. The emergent data shows, in a homologous mode with the human model, that the bovine integrins áVâ6 preferentially presents a unique hydrophobic interface (amino acids usage) which supports their specificity for the alfa helix presented at the end of the RGD peptide. Other IT subunits (â3 and â5) at the same interaction interface residues, present more polar or bulky amino acids which result in a less compatible interaction.In summary, our work builds on previous structures to recapitulate the bovine model and bring information concerning the specificity determinants of the recognition between FMDV and bovine integrins. We have also described the preferred sequence space of the bovine integrins for any peptide.