Structural Dynamics of the Cereblon Ligand Binding Domain
Fig 6
The thalidomide binding domain of mouse cereblon exhibits flexibility comparable to MsCI4.
The mouse domain in complex with (blue, sand) and without thalidomide (yellow, shades of brown) is compared to MsCI4•thalidomide (transparent white). (A) Two thalidomide-bound domains from 4TZC arranged as an intertwined dimer. (B) Superposition of one monomer to MsCI4•thalidomide, illustrating the unfolded nature of the first flexible region. (C) Same as (B) but from another perspective, in stereo. (D) Apo mouse domains in 3WX2 are found in two conformations, “yellow” and “brown”, forming an endless array of interactions in the crystal lattice. (E) Superposition of both apo conformations onto MsCI4•thalidomide, showing the first flexible region in different conformations. (F) Same as (E) but from another perspective, in stereo. Note that the conformation of the tryptophans on the left is reminiscent of the flipped tryptophan in the intertwined MsCI4 dimer.