Defining molecular glues with a dual-nanobody cannabidiol sensor.

ABSTRACT: "Molecular glue" (MG) is a term coined to describe the mechanism of action of the plant hormone auxin and subsequently used to characterize synthetic small molecule protein degraders exemplified by immune-modulatory imide drugs (IMiDs). Prospective development of MGs, however, has been hampered by its elusive definition and thermodynamic characteristics. Here, we report the crystal structure of a dual-nanobody cannabidiol-sensing system, in which the ligand promotes protein-protein interaction in a manner analogous to auxin. Through quantitative analyses, we draw close parallels among the dual-nanobody cannabidiol sensor, the auxin perception complex, and the IMiDs-bound CRL4^CRBN E3, which can bind and ubiquitinate "neo-substrates". All three systems, including the recruitment o

SUBMITTER: Cao S 

PROVIDER: S-EPMC8831599 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature