The Thalidomide-Binding Domain of Cereblon Defines the CULT Domain Family and Is a New Member of the β-Tent Fold
Figure 6
Structure gallery and evolutionary inference for proteins with a β-tent fold.
Only the core fold is shown; in structures where additional parts of the polypeptide chain obscured the view on the core fold, these were omitted. The β-strands of the insertion between β2 and β3 of the N-terminal β-meander is colored orange. The top image shows a superposition of the two halves of the MsrB structure 3HCJ (r.m.s.d. of 1 Å over the Cα carbons of the 30 superimposable residues) and the central image shows 3HCJ itself, as the most symmetrical of the β-tent structures. The images around the circumference show the seven domains of known structure discussed in this article (see also Fig. S2). Of these, DUF427 and TCTP systematically lack a zinc binding site, and MsrB homologs have occasionally lost it. In the other domains, the zinc binding site is essentially always present, although the cysteine pattern is slightly modified in GFA relative to all other domains, the first cysteine tandem being CxCxxx, rather than xxCxxC. The arrows in the figure show our inference for a possible evolutionary path. The fold could thus have originated by duplication of a four-stranded β-meander and subsequently diverged into the domains seen today. Where homologous relationships are supported by sequence similarity, the arrows are black; otherwise they are grey.