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bioRxiv · 10.64898/2025.12.18.695140

Structure of Factor VII Gla domain bound to EPCR

Lopez-Sagaseta, J.·Dichiara-Rodriguez, M. G.
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Abstract

The precise molecular determinants that underlie the binding of activated factor VII (FVIIa) to the endothelial cell protein C receptor (EPCR) have long remained unresolved. We report here the crystal structure of factor VII Gla domain bound to human EPCR, revealing a binding geometry in essence indistinguishable from that of the PC-EPCR interface and confirming absolute structural competition for EPCR binding. Relative to previous FVII structures, we observe receptor-dependent repositioning of the Gla {omega} loop coupled to a selective arrangement in which metal ion at position four adopts a Ca2+-compatible and EPCR-restricted coordination state. These findings resolve a long-standing gap and inform the structural basis for the binding of EPCR to FVIIa, a current therapeutic intervention in hemophilia.

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Lopez-Sagaseta, J., Dichiara-Rodriguez, M. G.. 2025-12-20. Structure of Factor VII Gla domain bound to EPCR. https://doi.org/10.64898/2025.12.18.695140

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