NF-κB ROB forms an intertwined homodimer

The X-ray structure of the ReIB dimerization domain (DD) reveals that the ReIBDD assumes an unexpected intertwined fold topology atypical of other NF-kappa B dimers. All typical NF-kappa B dimers are formed by the association of two independently folded immunoglobulin (Ig) domains. In ReIBDD, two polypeptides reconstruct both Ig domains in the dimer with an extra beta sheet connecting the two domains. Residues most critical to NF-kappa B dimer formation are invariant in ReIB, and Y300 plays a positive role in ReIBDD dimer formation. The presence of ReIB-specific nonpolar residues at the surface removes several intradomain surface hydrogen bonds that may render the domain fold unstable. Intertwining may stabilize the ReIBDD homodimer by forming the extra beta sheet. We show that, as in the crystal, ReIB forms an intertwined homodimer in solution. We suggest that the transiently stable ReIB homodimer might prevent its rapid degradation, allowing for heterodimer formation with p50 and p52.