Structure of EPCR in a non-canonical conformation

Lopez-Sagaseta, J.; Erausquin Arrondo, E.; Rodriguez Fernandez, A.

doi:10.1101/2021.12.16.472967

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bioRxiv · 10.1101/2021.12.16.472967

Structure of EPCR in a non-canonical conformation

Lopez-Sagaseta, J.·Erausquin Arrondo, E.·Rodriguez Fernandez, A.

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Abstract

Structural motion and conformational flexibility are often linked to biological functions of proteins. Whether the endothelial protein C receptor (EPCR), like other molecules, is vulnerable to folding transitions or might adopt alternative conformations remains unknown. The current understanding points to a rigid molecular structure suitable for binding of its ligands, like the anticoagulant protein C, or the CIDR1 domains of Plasmodium falciparum. In this study, we have identified a novel conformation of EPCR, captured by X-ray diffraction analyses, whereby Tyr154 shows a dramatically altered structural arrangement, likely incompatible with protein C binding. Biolayer interferometry analysis confirms previous results supporting a critical role for this position in protein C binding. Importantly, the conformational change has no apparent effect in the bound lipid. We conclude these findings reveal a site of conformational vulnerability in EPCR and inform a highly malleable region that could modulate EPCR functions.

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Lopez-Sagaseta, J., Erausquin Arrondo, E., Rodriguez Fernandez, A.. 2021-12-17. Structure of EPCR in a non-canonical conformation. https://doi.org/10.1101/2021.12.16.472967

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