Structural basis for tandem L27 domain-mediated polymerization.

Area of Science:

• Cell Biology
• Structural Biology
• Biochemistry

Background:

• Epithelial cell polarity is vital for tissue development and function.
• Multipro tein complexes, including scaffolding proteins like Dlg1, MPP7, and Mals3, are essential for establishing and maintaining cell polarity.
• These proteins interact via L27 domains to form functional complexes.

Purpose of the Study:

• To determine the crystal structure of the human tripartite complex Dlg1-MPP7-Mals3.
• To elucidate the role of L27 domains in the assembly of this complex.
• To understand the structural basis of apicobasal polarity establishment in epithelial tissues.

Main Methods:

• X-ray crystallography was used to obtain the structure of the 4-L27-domain complex.
• Paramagnetic relaxation enhancement (PRE) measurements were employed to study the complex in solution.
• Biochemical experiments were conducted to validate the structural findings.

Main Results:

• The crystal structure of the Dlg1-MPP7-Mals3 tripartite complex was determined.
• The complex comprises two pairs of heterodimeric L27 domains, exhibiting asymmetry.
• The C-terminal L27 domain of MPP7, specifically its loop αA-αB and helix αB, was identified as critical for complex assembly.

Conclusions:

• The Dlg1-MPP7-Mals3 complex forms a heterotrimer with a unique asymmetric structure.
• A synergistic mechanism involving tandem L27 domains mediates the assembly of the tripartite complex.
• Understanding this assembly mechanism provides insights into the regulation of epithelial cell polarity and morphogenesis.