Partial unfolding of MsCI4 upon loss of thalidomide.

<p>Crystals of the orthorhombic crystal from two crystallization conditions were washed for 40 h in a solution without thalidomide. For the initial structure (grey) and both experiments, “Wash I” (brown) and “Wash II” (black), the monomer that had the ligand washed out (chain C) is depicted in two perspectives. Loss of ligand was accompanied by the unfolding of three regions. The structures after washing are overlaid with the initial structure in transparent. On the bottom, the sequence alignment of MsCI4 with human cereblon details the unfolded regions and indicates secondary structure elements. The unfolded regions are shaded. In “Wash I”, the unfolding of the first region is incomplete, so the hairpin formed by the 3^rd and 4^th β-strand is still folded, albeit shifted in position. The C-terminal segment deleted in the R419X mutant of human cereblon and the corresponding segment in MsCI4 are underlined. Key-residues are highlighted red.