The FASEB Journal • Research Communication Structural basis for tandem L27 domain-mediated

ABSTRACT The establishment of epithelial cell po-larity requires the assembly of multiprotein complexes and is crucial during epithelial morphogenesis. Three scaffolding proteins, Dlg1, MPP7, and Mals3, can be assembled to form a complex that functions in the establishment and maintenance of apicobasal polarity in epithelial tissues through their L27 domains. Here we report the crystal structure of a 4-L27-domain complex derived from the human tripartite complex Dlg1-MPP7-Mals3 in combination with paramagnetic relaxation enhancement measurements. The heterotri-mer consists of 2 pairs of heterodimeric L27 domains. These 2 dimers are asymmetric due to the large differ-ence between the N- and C-terminal tandem L27 do-main of MPP7. Structural analysis combined with biochemical experiments further reveals that the loop A-B and helix B of the C-terminal L27 domain of MPP7 play a critical role in assembling the entire tripartite complex, suggesting a synergistic tandem L27-mediated assembling event.—Yang, X.