Structural basis for tandem L27 domain-mediated polymerization.
The establishment of epithelial cell polarity 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 heterotrimer consists of 2 pairs of heterodimeric L27 domains. These 2 dimers are asymmetric due to the large difference between the N- and C-terminal tandem L27 domain of MPP7. Structural analysis combined with biochemical experiments further reveals that the loop αA-αB and helix αB 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
Xue
X
Tianjin Key Laboratory of Protein Science, College of Life Science, Nankai University, Tianjin, China.
Xie
Xingqiao
X
Chen
Liu
L
Zhou
Hao
H
Wang
Zheng
Z
Zhao
Weijing
W
Tian
Ran
R
Zhang
Rongguang
R
Tian
Changlin
C
Long
Jiafu
J
Shen
Yuequan
Y
D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016764:Cell Polarity / Q000502:physiology; D000074288:Discs Large Homolog 1 Protein; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000235:genetics / Q000502:physiology; D055503:Protein Multimerization / Q000235:genetics / Q000502:physiology; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary / Q000235:genetics / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; C513314:DLG1 protein, human; D000074288:Discs Large Homolog 1 Protein; C486531:LIN7C protein, human; C482290:MPP7 protein, human; D008565:Membrane Proteins; D046912:Multiprotein Complexes