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Structural Biology of the Immune Checkpoint Receptor PD-1 and Its Ligands PD-L1/PD-L2

Zak, K. M., Grudnik, P., Magiera, K., Dömling, A., Dubin, G. & Holak, T. A., 1-Aug-2017, In : Structure. 25, 8, p. 1163-1174 12 p.

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  • Structural Biology of the Immune Checkpoint Receptor PD-1 and Its Ligands PD-L1/PD-L2

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DOI

  • Krzysztof M. Zak
  • Przemyslaw Grudnik
  • Katarzyna Magiera
  • Alexander Dömling
  • Grzegorz Dubin
  • Tad A. Holak

Cancer cells can avoid and suppress immune responses through activation of inhibitory immune checkpoint proteins, such as PD-1, PD-L1, and CTLA-4. Blocking the activities of these proteins with monoclonal antibodies, and thus restoring T cell function, has delivered breakthrough therapies against cancer. In this review, we describe the latest work on structural characterization of the checkpoint proteins, their interactions with cognate ligands and with therapeutic antibodies. Structures of the extracellular portions of these proteins reveal that they all have a similar modular structure, composed of small domains similar in topology to the domains found in antibodies. Structural basis for blocking the PD-1/PD-L1 interaction by small molecules is illustrated with the compound BMS-202 that binds to and induces dimerization of PD-L1.

Original languageEnglish
Pages (from-to)1163-1174
Number of pages12
JournalStructure
Volume25
Issue number8
Publication statusPublished - 1-Aug-2017

    Keywords

  • PROGRAMMED DEATH 1, CANCER-IMMUNOTHERAPY, COMBINATION IMMUNOTHERAPY, ANTIBODY PEMBROLIZUMAB, CRYSTAL-STRUCTURE, BREAST-CANCER, B7 FAMILY, BLOCKADE, THERAPY, COMPLEX

ID: 46569396