7Q5D

Structure of EPCR in a non-canonical conformation

Summary for 7Q5D

• Entry DOI: 10.2210/pdb7q5d/pdb
• Descriptor: Endothelial protein C receptor, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, CYSTEINE, ... (6 entities in total)
• Functional Keywords: endothelium, mhc-i-like, lipid receptor, conformational change, blood clotting
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 23996.82

Authors

Lopez-Sagaseta, J.,Erausquin, E. (deposition date: 2021-11-03, release date: 2022-09-14, Last modification date: 2026-08-12)

Primary citation

Erausquin, E.,Rodriguez-Fernandez, A.,Rodriguez-Lumbreras, L.A.,Fernandez-Recio, J.,Dichiara-Rodriguez, M.G.,Lopez-Sagaseta, J.
Structural vulnerability in EPCR suggests functional modulation.
Sci Rep, 14:2591-2591, 2024

PubMed Abstract: The endothelial protein C receptor (EPCR) is a fundamental component of the vascular system in mammals due to its contribution in maintaining blood in a non-prothrombotic state, which is crucial for overall life development. It accomplishes this by enhancing the conversion of protein C (PC) into the anticoagulant activated protein C (APC), with this property being dependent on a known EPCR conformation that enables direct interaction with PC/APC. In this study, we report a previously unidentified conformation of EPCR whereby Tyr154, critical for PC/APC binding, shows a striking non-canonical configuration. This unconventional form is incompatible with PC/APC binding, and reveals, for the first time, a region of structural vulnerability and potential modulation in EPCR. The identification of this malleability enhances our understanding of this receptor, prompting inquiries into the interplay between its plasticity and function, as well as its significance within the broader framework of EPCR's biology, which extends to immune conditions.

PubMed: 38297105
DOI: 10.1038/s41598-024-53160-7

Experimental method

X-RAY DIFFRACTION (1.8 Å)