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Structural biology

Insights into platelet pharmacology from a cryo-EM structure of the ABCC4 transporter

Nature Cardiovascular Research volume 2, pages 606–608 (2023)Cite this article

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Structural determination of the ABCC4 transporter is a major first step in providing crucial molecular insights into the transport of platelet substrates into granules, as well as drug transport from platelets. The findings provide a framework for understanding platelet interactions and potential design of specific platelet antagonists.

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Fig. 1: Proposed mechanism of ABCC4-mediated transport of platelet substrates and inhibitors.
Fig. 2: Competitive inhibition of ABCC4-mediated aspirin transport by dipyridamole.

References

  1. Antithrombotic Trialists' Collaboration. BMJ 324, 71–86 (2002).

    Article  Google Scholar 

  2. McFadyen, J. D., Schaff, M. & Peter, K. Nat. Rev. Cardiol. 15, 181–191 (2018).

    Article  CAS  PubMed  Google Scholar 

  3. Gorog, D. A., Sweeny, J. M. & Fuster, V. Nat. Rev. Cardiol. 6, 365–373 (2009).

    Article  CAS  PubMed  Google Scholar 

  4. Sweeny, J. M., Gorog, D. A. & Fuster, V. Nat. Rev. Cardiol. 6, 273–282 (2009).

    Article  CAS  PubMed  Google Scholar 

  5. Vasiliou, V., Vasiliou, K. & Nebert, D. W. Hum. Genomics 3, 281–290 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Thomas, C. & Tampe, R. Annu. Rev. Biochem. 89, 60–636 (2020).

    Article  Google Scholar 

  7. Cheepala, S. B. et al. Blood 126, 2307–2319 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Jedlitschky, G., Greinacher, A. & Kroemer, H. K. Blood 119, 3394–3402 (2012).

    Article  CAS  PubMed  Google Scholar 

  9. Reid, G. et al. Proc. Natl Acad. Sci. USA 100, 9244–9249 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Russel, F. G., Koenderink, J. B. & Masereeuw, R. Trends Pharmacol. Sci. 29, 200–207 (2008).

    Article  CAS  PubMed  Google Scholar 

  11. Mattiello, T. et al. J. Am. Coll. Cardiol. 58, 752–761 (2011).

    Article  CAS  PubMed  Google Scholar 

  12. Cheung, L. et al. Biochem. Pharmacol. 93, 380–388 (2015).

    Article  CAS  PubMed  Google Scholar 

  13. Chen, Y. et al. Nat. Cardiovas. Res. https://doi.org/10.1038/s44161-023-00289-9 (2023).

    Article  Google Scholar 

  14. Tyagi, T. et al. Nat. Cardiovas. Res. 1, 223–237 (2022).

    Article  Google Scholar 

Download references

Acknowledgements

This work was funded by National Institutes of Health (NIH) National Heart, Lung, and Blood Institute (NHLBI) (R01-HL122815, R01-HL150515 and R01-HL115247) to J.H., a K08 award to A.S. (K08-HL150246), and a T32 to S.X.G. (T32-HL007974).

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Authors and Affiliations

  1. Section of Hematology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA

    Anish V. Sharda

  2. Department of Laboratory Medicine, Yale University School of Medicine, Yale New Haven Hospital, New Haven, CT, USA

    Sean X. Gu

  3. Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA

    John Hwa

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  1. Anish V. Sharda
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  2. Sean X. Gu
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  3. John Hwa
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Correspondence to John Hwa.

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Sharda, A.V., Gu, S.X. & Hwa, J. Insights into platelet pharmacology from a cryo-EM structure of the ABCC4 transporter. Nat Cardiovasc Res 2, 606–608 (2023). https://doi.org/10.1038/s44161-023-00293-z

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