Structure of mouse muskelin discoidin domain and biochemical characterization of its self-association

Muskelin is an intracellular kelch‐repeat protein comprised of discoidin, LisH, CTLH and kelch‐repeat domains. It is involved in cell adhesion and the regulation of cytoskeleton dynamics as well as being a component of a putative E3 ligase complex. Here, the first crystal structure of mouse muskelin discoidin domain (MK‐DD) is reported at 1.55 Å resolution, which reveals a distorted eight‐stranded β‐barrel with two short α‐helices at one end of the barrel. Interestingly, the N‐ and C‐termini are not linked by the disulfide bonds found in other eukaryotic discoidin structures. A highly conserved MIND motif appears to be the determinant for MK‐DD specific interaction together with the spike loops. Analysis of interdomain interaction shows that MK‐DD binds the kelch‐repeat domain directly and that this interaction depends on the presence of the LisH domain.