7RGA

Crystal structure of nanoCLAMP3:VHH in complex with MTX

7RGA の概要

• エントリーDOI: 10.2210/pdb7rga/pdb
• 分子名称: nano CLostridial Antibody Mimetic Protein 3 VHH, METHOTREXATE, SODIUM ION, ... (4 entities in total)
• 機能のキーワード: immune system
• 由来する生物種: synthetic construct
• タンパク質・核酸の鎖数: 7
• 化学式量合計: 232000.16

構造登録者

Guo, Z.,Alexandrov, K. (登録日: 2021-07-14, 公開日: 2022-05-25, 最終更新日: 2023-10-18)

主引用文献

Guo, Z.,Smutok, O.,Johnston, W.A.,Walden, P.,Ungerer, J.P.J.,Peat, T.S.,Newman, J.,Parker, J.,Nebl, T.,Hepburn, C.,Melman, A.,Suderman, R.J.,Katz, E.,Alexandrov, K.
Design of a methotrexate-controlled chemical dimerization system and its use in bio-electronic devices.
Nat Commun, 12:7137-7137, 2021

PubMed Abstract: Natural evolution produced polypeptides that selectively recognize chemical entities and their polymers, ranging from ions to proteins and nucleic acids. Such selective interactions serve as entry points to biological signaling and metabolic pathways. The ability to engineer artificial versions of such entry points is a key goal of synthetic biology, bioengineering and bioelectronics. We set out to map the optimal strategy for developing artificial small molecule:protein complexes that function as chemically induced dimerization (CID) systems. Using several starting points, we evolved CID systems controlled by a therapeutic drug methotrexate. Biophysical and structural analysis of methotrexate-controlled CID system reveals the critical role played by drug-induced conformational change in ligand-controlled protein complex assembly. We demonstrate utility of the developed CID by constructing electrochemical biosensors of methotrexate that enable quantification of methotrexate in human serum. Furthermore, using the methotrexate and functionally related biosensor of rapamycin we developed a multiplexed bioelectronic system that can perform repeated measurements of multiple analytes. The presented results open the door for construction of genetically encoded signaling systems for use in bioelectronics and diagnostics, as well as metabolic and signaling network engineering.

PubMed: 34880210
DOI: 10.1038/s41467-021-27184-w

実験手法

X-RAY DIFFRACTION (2.9 Å)