Structural in silico dissection of the collagen V interactome to identify genotype-phenotype correlations in classic Ehlers-Danlos Syndrome (EDS)

Collagen V mutations are associated with Elhers-Danlos syndrome (EDS), a group of heritable collagenopathies. Collagen V structure is not available and the disease-causing mechanism is unclear. To address this issue, we manually curated missense mutations suspected to promote classic type EDS (cEDS) insurgence from the literature and performed a genotype-phenotype correlation study. Further, we generated a homology model of the collagen V triple helix to evaluate the pathogenic effects. The resulting structure was used to map known protein-protein interactions enriched with in silico predictions. An interaction network model for collagen V was created. We found that cEDS heterogeneous manifestations may be explained by the involvement in two different extracellular matrix pathways, related to cell adhesion and tissue repair or cell differentiation, growth and apoptosis.