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. 2021 Dec 8;12:7137. doi: 10.1038/s41467-021-27184-w

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — a Graphic representation of a dimerizing system that relies on formation of a new interface including an anchor protein and small molecule. The second binder recognizes this interface in a ligand-dependent way. b Dimerizing system where ligand binding leads to a conformation change of the anchor domain that is recognized by the second binder. c Ribbon representation of dihydrofolate reductase:methotrexate complex (PDB:1DDS). d thymidylate synthase:methotrexate complex (PDB:1AXW). e VHH: methotrexate complex (PDB:3QXV) displayed as white ribbon. Methotrexate is displayed in ball and stick representation with atomic colors.