Related Experiment Video

Updated: Jun 15, 2025

An In Vitro Assay to Study Platelet Migration Using RGD-Functionalized Avidin-Biotin Tethers
05:43

An In Vitro Assay to Study Platelet Migration Using RGD-Functionalized Avidin-Biotin Tethers

Published on: November 8, 2024

281

Structural insights into human ABCC4-mediated transport of platelet agonist and antagonist

Yu Chen1,2,3, Liang Wang2,3, Wen-Tao Hou2,3

  • 1Department of Endocrinology, Institute of Endocrine and Metabolic Diseases, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

Nature Cardiovascular Research
|August 28, 2024
PubMed

Human platelets contribute to hemostasis and thrombosis, the imbalance of which can cause cardiovascular diseases. The activation and accumulation of platelets can be induced by agonists or inhibited by antagonists. Thus, the human ABC transporter ABCC4, which pumps out platelet agonists and antagonists, might become a promising target for preventing cardiovascular diseases. Here we define five structures of human ABCC4: the apo and three complexed forms in the inward-facing conformation, in addition to an outward-facing occluded conformation upon ATP binding. Combined with biochemical assays, we structurally prove that U46619, a synthetic analog of the unstable agonist TXA2, and the antagonist aspirin are substrates of ABCC4. In addition, we found that the platelet antagonist dipyridamole is a strong competitive inhibitor against ABCC4. These complex structures also enable us to identify a transmembrane pocket in ABCC4 that provides a defined space for the rational design of specific platelet antagonists.

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