title: Structural basis for tandem L27 domain-mediated polymerization.
abstract: 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.
authors: Tianjin Key Laboratory of Protein Science, College of Life Science, Nankai University, Tianjin, China.
authors: Xue
authors: X
authors: Yang
authors: Xingqiao
authors: X
authors: Xie
authors: Liu
authors: L
authors: Chen
authors: Hao
authors: H
authors: Zhou
authors: Zheng
authors: Z
authors: Wang
authors: Weijing
authors: W
authors: Zhao
authors: Ran
authors: R
authors: Tian
authors: Rongguang
authors: R
authors: Zhang
authors: Changlin
authors: C
authors: Tian
authors: Jiafu
authors: J
authors: Long
authors: Yuequan
authors: Y
authors: Shen
mesh_terms: 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
chemical_list: 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