{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:14:24Z","timestamp":1790640864381,"version":"4.1.0"},"reference-count":54,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,8,30]],"date-time":"2022-08-30T00:00:00Z","timestamp":1661817600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,8,30]],"date-time":"2022-08-30T00:00:00Z","timestamp":1661817600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Commun Biol"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Whether membrane-anchored PD-L1 homodimerizes in living cells is controversial. The biological significance of the homodimer waits to be expeditiously explored. However, characterization of the membrane-anchored full-length PD-L1 homodimer is challenging, and unconventional approaches are needed. By using genetically incorporated crosslinkers, we showed that full length PD-L1 forms homodimers and tetramers in living cells. Importantly, the homodimerized intracellular domains of PD-L1 play critical roles in its complex glycosylation. Further analysis identified three key arginine residues in the intracellular domain of PD-L1 as the regulating unit. In the PD-L1\/PD-L1-3RE homodimer, mutations result in a decrease in the membrane abundance and an increase in the Golgi of wild-type PD-L1. Notably, PD-1 binding to abnormally glycosylated PD-L1 on cancer cells was attenuated, and subsequent T-cell induced toxicity increased. Collectively, our study demonstrated that PD-L1 indeed forms homodimers in cells, and the homodimers play important roles in PD-L1 complex glycosylation and T-cell mediated toxicity.<\/jats:p>","DOI":"10.1038\/s42003-022-03845-4","type":"journal-article","created":{"date-parts":[[2022,8,30]],"date-time":"2022-08-30T14:05:36Z","timestamp":1661868336000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Homodimerized cytoplasmic domain of PD-L1 regulates its complex glycosylation in living cells"],"prefix":"10.1038","volume":"5","author":[{"given":"Li","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangni","family":"Chai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihui","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shupan","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueyin","family":"Zu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanping","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aolan","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueyun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9995-3255","authenticated-orcid":false,"given":"Haiyan","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,8,30]]},"reference":[{"key":"3845_CR1","doi-asserted-by":"publisher","first-page":"1537","DOI":"10.1182\/blood-2008-12-195792","volume":"114","author":"M Ahmadzadeh","year":"2009","unstructured":"Ahmadzadeh, M. et al. Tumor antigen-specific CD8 T cells infiltrating the tumor express high levels of PD-1 and are functionally impaired. Blood 114, 1537\u20131544 (2009).","journal-title":"Blood"},{"key":"3845_CR2","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1038\/nature14011","volume":"515","author":"RS Herbst","year":"2014","unstructured":"Herbst, R. S. et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature 515, 563\u2013567 (2014).","journal-title":"Nature"},{"key":"3845_CR3","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1126\/science.aaa8172","volume":"348","author":"P Sharma","year":"2015","unstructured":"Sharma, P. & Allison, J. P. The future of immune checkpoint therapy. Science 348, 56\u201361 (2015).","journal-title":"Science"},{"key":"3845_CR4","doi-asserted-by":"publisher","first-page":"1767","DOI":"10.1056\/NEJMra1514296","volume":"375","author":"VA Boussiotis","year":"2016","unstructured":"Boussiotis, V. A. Molecular and biochemical aspects of the PD-1 checkpoint pathway. N. Engl. J. Med. 375, 1767\u20131778 (2016).","journal-title":"N. Engl. J. Med."},{"key":"3845_CR5","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1056\/NEJMoa1412082","volume":"372","author":"C Robert","year":"2015","unstructured":"Robert, C. et al. Nivolumab in previously untreated melanoma without BRAF mutation. N. Engl. J. Med. 372, 320\u2013330 (2015).","journal-title":"N. Engl. J. Med."},{"key":"3845_CR6","doi-asserted-by":"crossref","unstructured":"Schachter, J. et al. Pembrolizumab versus ipilimumab for advanced melanoma: final overall survival results of a multicentre, randomised, open-label phase 3 study (KEYNOTE-006). Lancet 390, 1853\u20131862 (2017).","DOI":"10.1016\/S0140-6736(17)31601-X"},{"key":"3845_CR7","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1056\/NEJMoa1411087","volume":"372","author":"SM Ansell","year":"2015","unstructured":"Ansell, S. M. et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin\u2019s lymphoma. N. Engl. J. Med. 372, 311\u2013319 (2015).","journal-title":"N. Engl. J. Med."},{"key":"3845_CR8","doi-asserted-by":"publisher","unstructured":"Kammerer-Jacquet, S. F. et al. Targeting the PD-1\/PD-L1 pathway in renal cell carcinoma. Int. J. Mol. Sci. 20, https:\/\/doi.org\/10.3390\/ijms20071692 (2019).","DOI":"10.3390\/ijms20071692"},{"key":"3845_CR9","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1016\/S1470-2045(15)70054-9","volume":"16","author":"NA Rizvi","year":"2015","unstructured":"Rizvi, N. A. et al. Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial. Lancet Oncol. 16, 257\u2013265 (2015).","journal-title":"Lancet Oncol."},{"key":"3845_CR10","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1056\/NEJMoa1613683","volume":"376","author":"J Bellmunt","year":"2017","unstructured":"Bellmunt, J. et al. Pembrolizumab as second-line therapy for advanced urothelial carcinoma. N. Engl. J. Med. 376, 1015\u20131026 (2017).","journal-title":"N. Engl. J. Med."},{"key":"3845_CR11","doi-asserted-by":"publisher","first-page":"2455","DOI":"10.1056\/NEJMoa1200694","volume":"366","author":"JR Brahmer","year":"2012","unstructured":"Brahmer, J. R. et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N. Engl. J. Med. 366, 2455\u20132465 (2012).","journal-title":"N. Engl. J. Med."},{"key":"3845_CR12","doi-asserted-by":"crossref","unstructured":"Shaabani, S. et al. A patent review on PD-1\/PD-L1 antagonists: small molecules, peptides, and macrocycles (2015-2018). Expert Opin. Ther. Patent 28, 665\u2013678 (2018).","DOI":"10.1080\/13543776.2018.1512706"},{"key":"3845_CR13","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/j.ccell.2018.01.009","volume":"33","author":"CW Li","year":"2018","unstructured":"Li, C. W. et al. Eradication of triple-negative breast cancer cells by targeting glycosylated PD-L1. Cancer Cell 33, 187\u2013201.e110 (2018).","journal-title":"Cancer Cell"},{"key":"3845_CR14","doi-asserted-by":"publisher","unstructured":"Wang, H. et al. HIP1R targets PD-L1 to lysosomal degradation to alter T cell-mediated cytotoxicity. Nat. Chem. Biol. https:\/\/doi.org\/10.1038\/s41589-018-0161-x (2018).","DOI":"10.1038\/s41589-018-0161-x"},{"key":"3845_CR15","doi-asserted-by":"publisher","first-page":"1365","DOI":"10.1038\/70932","volume":"5","author":"D Haidong","year":"1999","unstructured":"Haidong, D., Gefeng, Z., Koji, T. & Chen, L. B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nat. Med. 5, 1365\u20131369 (1999).","journal-title":"Nat. Med."},{"key":"3845_CR16","doi-asserted-by":"crossref","unstructured":"Zak, K. M. et al. Structural basis for small molecule targeting of the programmed death ligand 1 (PD-L1. Oncotarget 7, 30323\u201330335 (2016).","DOI":"10.18632\/oncotarget.8730"},{"key":"3845_CR17","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1007\/s13238-010-0022-1","volume":"1","author":"Y Chen","year":"2010","unstructured":"Chen, Y. et al. A dimeric structure of PD-L1: functional units or evolutionary relics. Protein Cell 1, 153\u2013160 (2010).","journal-title":"Protein Cell"},{"key":"3845_CR18","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms12632","volume":"7","author":"CW Li","year":"2016","unstructured":"Li, C. W. et al. Glycosylation and stabilization of programmed death ligand-1 suppresses T-cell activity. Nat. Commun. 7, 12632 (2016).","journal-title":"Nat. Commun."},{"key":"3845_CR19","doi-asserted-by":"publisher","first-page":"925","DOI":"10.1016\/j.ccell.2016.10.010","volume":"30","author":"SO Lim","year":"2016","unstructured":"Lim, S. O. et al. Deubiquitination and Stabilization of PD-L1 by CSN5. Cancer Cell 30, 925\u2013939 (2016).","journal-title":"Cancer Cell"},{"key":"3845_CR20","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1038\/s41422-018-0124-5","volume":"29","author":"Y Yang","year":"2019","unstructured":"Yang, Y. et al. Palmitoylation stabilizes PD-L1 to promote breast tumor growth. Cell Res. 29, 83\u201386 (2019).","journal-title":"Cell Res."},{"key":"3845_CR21","doi-asserted-by":"publisher","unstructured":"Zhu, D. et al. Deubiquitinating enzyme OTUB1 promotes cancer cell immunosuppression via preventing ER-associated degradation of immune checkpoint protein PD-L1. Cell Death Differ. https:\/\/doi.org\/10.1038\/s41418-020-00700-z (2020).","DOI":"10.1038\/s41418-020-00700-z"},{"key":"3845_CR22","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1038\/s41551-019-0375-6","volume":"3","author":"H Yao","year":"2019","unstructured":"Yao, H. et al. Inhibiting PD-L1 palmitoylation enhances T-cell immune responses against tumours. Nat. Biomed. Eng. 3, 306\u2013317 (2019).","journal-title":"Nat. Biomed. Eng."},{"key":"3845_CR23","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-02409-z","volume":"8","author":"B Yang","year":"2017","unstructured":"Yang, B. et al. Spontaneous and specific chemical cross-linking in live cells to capture and identify protein interactions. Nat. Commun. 8, 2240 (2017).","journal-title":"Nat. Commun."},{"key":"3845_CR24","doi-asserted-by":"publisher","first-page":"15737","DOI":"10.1002\/anie.201706927","volume":"56","author":"M Cigler","year":"2017","unstructured":"Cigler, M. et al. Proximity-triggered covalent stabilization of low-affinity protein complexes in vitro and in vivo. Angew. Chem. Int. Ed. 56, 15737\u201315741 (2017).","journal-title":"Angew. Chem. Int. Ed."},{"key":"3845_CR25","doi-asserted-by":"publisher","first-page":"13253","DOI":"10.1021\/jacs.8b06922","volume":"140","author":"H Tang","year":"2018","unstructured":"Tang, H. et al. Proteomic identification of protein tyrosine phosphatase and substrate interactions in living mammalian cells by genetic encoding of irreversible enzyme inhibitors. J. Am. Chem. Soc. 140, 13253\u201313259 (2018).","journal-title":"J. Am. Chem. Soc."},{"key":"3845_CR26","doi-asserted-by":"publisher","first-page":"885","DOI":"10.1038\/nmeth.2595","volume":"10","author":"Z Xiang","year":"2013","unstructured":"Xiang, Z. et al. Adding an unnatural covalent bond to proteins through proximity-enhanced bioreactivity. Nat. Methods 10, 885\u2013888 (2013).","journal-title":"Nat. Methods"},{"key":"3845_CR27","doi-asserted-by":"publisher","first-page":"2190","DOI":"10.1002\/anie.201308794","volume":"53","author":"Z Xiang","year":"2014","unstructured":"Xiang, Z. et al. Proximity-enabled protein crosslinking through genetically encoding haloalkane unnatural amino acids. Angew. Chem. Int. Ed. 53, 2190\u20132193 (2014).","journal-title":"Angew. Chem. Int. Ed."},{"key":"3845_CR28","doi-asserted-by":"publisher","first-page":"1807","DOI":"10.1042\/BST20200508","volume":"48","author":"H Ren","year":"2020","unstructured":"Ren, H. Genetically encoded selective cross-linkers and emerging applications. Biochem Soc. Trans. 48, 1807\u20131817 (2020).","journal-title":"Biochem Soc. Trans."},{"key":"3845_CR29","doi-asserted-by":"publisher","first-page":"6349","DOI":"10.1158\/0008-5472.CAN-18-1892","volume":"78","author":"JM Hsu","year":"2018","unstructured":"Hsu, J. M., Li, C. W., Lai, Y. J. & Hung, M. C. Posttranslational modifications of PD-L1 and their applications in cancer therapy. Cancer Re.s 78, 6349\u20136353 (2018).","journal-title":"Cancer Re.s"},{"key":"3845_CR30","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1186\/s12929-020-00670-x","volume":"27","author":"YN Wang","year":"2020","unstructured":"Wang, Y. N., Lee, H. H., Hsu, J. L., Yu, D. & Hung, M. C. The impact of PD-L1 N-linked glycosylation on cancer therapy and clinical diagnosis. J. Biomed. Sci. 27, 77 (2020).","journal-title":"J. Biomed. Sci."},{"key":"3845_CR31","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1111\/j.1432-1033.2004.04407.x","volume":"272","author":"G Mei","year":"2005","unstructured":"Mei, G., Di Venere, A., Rosato, N. & Finazzi-Agro, A. The importance of being dimeric. FEBS J. 272, 16\u201327 (2005).","journal-title":"FEBS J."},{"key":"3845_CR32","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms8354","volume":"6","author":"Z Ahmed","year":"2015","unstructured":"Ahmed, Z. et al. Grb2 monomer-dimer equilibrium determines normal versus oncogenic function. Nat. Commun. 6, 7354 (2015).","journal-title":"Nat. Commun."},{"key":"3845_CR33","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1038\/nchembio.1711","volume":"11","author":"L Xue","year":"2015","unstructured":"Xue, L. et al. Major ligand-induced rearrangement of the heptahelical domain interface in a GPCR dimer. Nat. Chem. Biol. 11, 134\u2013140 (2015).","journal-title":"Nat. Chem. Biol."},{"key":"3845_CR34","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9395","volume":"6","author":"Y Zhou","year":"2015","unstructured":"Zhou, Y. et al. STIM1 dimers undergo unimolecular coupling to activate Orai1 channels. Nat. Commun. 6, 8395 (2015).","journal-title":"Nat. Commun."},{"key":"3845_CR35","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13307","volume":"7","author":"SR Needham","year":"2016","unstructured":"Needham, S. R. et al. EGFR oligomerization organizes kinase-active dimers into competent signalling platforms. Nat. Commun. 7, 13307 (2016).","journal-title":"Nat. Commun."},{"key":"3845_CR36","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10262","volume":"7","author":"S Sarabipour","year":"2016","unstructured":"Sarabipour, S. & Hristova, K. Mechanism of FGF receptor dimerization and activation. Nat. Commun. 7, 10262 (2016).","journal-title":"Nat. Commun."},{"key":"3845_CR37","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01103-4","volume":"8","author":"E Deyaert","year":"2017","unstructured":"Deyaert, E. et al. A homologue of the Parkinson\u2019s disease-associated protein LRRK2 undergoes a monomer-dimer transition during GTP turnover. Nat. Commun. 8, 1008 (2017).","journal-title":"Nat. Commun."},{"key":"3845_CR38","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-03727-6","volume":"9","author":"PM Dijkman","year":"2018","unstructured":"Dijkman, P. M. et al. Dynamic tuneable G protein-coupled receptor monomer-dimer populations. Nat. Commun. 9, 1710 (2018).","journal-title":"Nat. Commun."},{"key":"3845_CR39","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-07510-5","volume":"9","author":"B Liu","year":"2018","unstructured":"Liu, B., Sureda-Gomez, M., Zhen, Y., Amador, V. & Reverter, D. A quaternary tetramer assembly inhibits the deubiquitinating activity of USP25. Nat. Commun. 9, 4973 (2018).","journal-title":"Nat. Commun."},{"key":"3845_CR40","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-10001-w","volume":"10","author":"YN Chang","year":"2019","unstructured":"Chang, Y. N. et al. Structural basis for functional interactions in dimers of SLC26 transporters. Nat. Commun. 10, 2032 (2019).","journal-title":"Nat. Commun."},{"key":"3845_CR41","doi-asserted-by":"publisher","first-page":"113821","DOI":"10.1016\/j.bcp.2020.113821","volume":"174","author":"C Bailly","year":"2020","unstructured":"Bailly, C. & Vergoten, G. Protein homodimer sequestration with small molecules: Focus on PD-L1. Biochem Pharm. 174, 113821 (2020).","journal-title":"Biochem Pharm."},{"key":"3845_CR42","doi-asserted-by":"publisher","unstructured":"Bartoschek, M. D. et al. Identification of permissive amber suppression sites for efficient non-canonical amino acid incorporation in mammalian cells. Nucleic Acids Res. https:\/\/doi.org\/10.1093\/nar\/gkab132 (2021).","DOI":"10.1093\/nar\/gkab132"},{"key":"3845_CR43","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1038\/nature24031","volume":"550","author":"JW Chin","year":"2017","unstructured":"Chin, J. W. Expanding and reprogramming the genetic code. Nature 550, 53\u201360 (2017).","journal-title":"Nature"},{"key":"3845_CR44","doi-asserted-by":"publisher","first-page":"1784","DOI":"10.1038\/nprot.2009.188","volume":"4","author":"CC Liu","year":"2009","unstructured":"Liu, C. C., Cellitti, S. E., Geierstanger, B. H. & Schultz, P. G. Efficient expression of tyrosine-sulfated proteins in E. coli using an expanded genetic code. Nat. Protoc. 4, 1784\u20131789 (2009).","journal-title":"Nat. Protoc."},{"key":"3845_CR45","doi-asserted-by":"publisher","first-page":"5857","DOI":"10.1021\/acs.jmedchem.7b00293","volume":"60","author":"K Guzik","year":"2017","unstructured":"Guzik, K. et al. Small-molecule inhibitors of the programmed cell death-1\/programmed death-ligand 1 (PD-1\/PD-L1) interaction via transiently induced protein states and dimerization of PD-L1. J. Med. Chem. 60, 5857\u20135867 (2017).","journal-title":"J. Med. Chem."},{"key":"3845_CR46","doi-asserted-by":"publisher","first-page":"1956","DOI":"10.1021\/cb500453a","volume":"9","author":"XH Chen","year":"2014","unstructured":"Chen, X. H. et al. Genetically encoding an electrophilic amino acid for protein stapling and covalent binding to native receptors. ACS Chem. Biol. 9, 1956\u20131961 (2014).","journal-title":"ACS Chem. Biol."},{"key":"3845_CR47","doi-asserted-by":"publisher","first-page":"e69047","DOI":"10.7554\/eLife.69047","volume":"10","author":"J Li","year":"2021","unstructured":"Li, J. et al. Genetically incorporated crosslinkers reveal NleE attenuates host autophagy dependent on PSMD10. eLife 10, e69047 (2021).","journal-title":"eLife"},{"key":"3845_CR48","doi-asserted-by":"publisher","first-page":"1818","DOI":"10.1016\/j.celrep.2017.07.075","volume":"20","author":"M Gato-Canas","year":"2017","unstructured":"Gato-Canas, M. et al. PDL1 signals through conserved sequence motifs to overcome interferon-mediated cytotoxicity. Cell Rep. 20, 1818\u20131829 (2017).","journal-title":"Cell Rep."},{"key":"3845_CR49","doi-asserted-by":"publisher","first-page":"1064","DOI":"10.1038\/s41556-020-0562-4","volume":"22","author":"Y Gao","year":"2020","unstructured":"Gao, Y. et al. Acetylation-dependent regulation of PD-L1 nuclear translocation dictates the efficacy of anti-PD-1 immunotherapy. Nat. Cell Biol. 22, 1064\u20131075 (2020).","journal-title":"Nat. Cell Biol."},{"key":"3845_CR50","doi-asserted-by":"publisher","unstructured":"Wen, M. et al. PD-L1 degradation is regulated by electrostatic membrane association of its cytoplasmic domain. Nat. Commun. 12, https:\/\/doi.org\/10.1038\/s41467-021-25416-7 (2021).","DOI":"10.1038\/s41467-021-25416-7"},{"key":"3845_CR51","doi-asserted-by":"publisher","first-page":"3011","DOI":"10.1073\/pnas.0712278105","volume":"105","author":"L David Yin-Wei","year":"2008","unstructured":"David Yin-Wei, L. et al. The PD-1\/PD-L1 complex resembles the antigen-binding Fv domains of antibodies and T cell receptors. Proc. Natl Acad. Sci. USA 105, 3011\u20133016 (2008).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"3845_CR52","doi-asserted-by":"crossref","unstructured":"Zhang, X., Schwartz, J. C. D., Almo, S. C., & Nathenson, S. G. Crystal structure of the receptor-binding domain of human B7-2: insights into organization and signaling. Proc. Natl Acad. Sci. USA 100, 2586\u20132591 (2003).","DOI":"10.1073\/pnas.252771499"},{"key":"3845_CR53","doi-asserted-by":"publisher","first-page":"881","DOI":"10.1093\/intimm\/dxm059","volume":"19","author":"S Terawaki","year":"2007","unstructured":"Terawaki, S. et al. Specific and high-affinity binding of tetramerized PD-L1 extracellular domain to PD-1-expressing cells: possible application to enhance T cell function. Int. Immunol. 19, 881\u2013890 (2007).","journal-title":"Int. Immunol."},{"key":"3845_CR54","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1126\/science.1231143","volume":"339","author":"C Le","year":"2013","unstructured":"Le, C. et al. Multiplex genome engineering using CRISPR\/Cas systems. Science 339, 819\u2013823 (2013).","journal-title":"Science"}],"container-title":["Communications Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s42003-022-03845-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-022-03845-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-022-03845-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,31]],"date-time":"2022-08-31T04:09:50Z","timestamp":1661918990000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s42003-022-03845-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,30]]},"references-count":54,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["3845"],"URL":"https:\/\/doi.org\/10.1038\/s42003-022-03845-4","relation":{},"ISSN":["2399-3642"],"issn-type":[{"value":"2399-3642","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,30]]},"assertion":[{"value":"5 April 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 August 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 August 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"887"}}