title: Structure of an L27 domain heterotrimer from cell polarity complex Patj/Pals1/Mals2 reveals mutually independent L27 domain assembly mode.
abstract: The assembly of supramolecular complexes in multidomain scaffold proteins is crucial for the control of cell polarity. The scaffold protein of protein associated with Lin-7 1 (Pals1) forms a complex with two other scaffold proteins, Pals-associated tight junction protein (Patj) and mammalian homolog-2 of Lin-7 (Mals2), through its tandem Lin-2 and Lin-7 (L27) domains to regulate apical-basal polarity. Here, we report the crystal structure of a 4-L27 domain-containing heterotrimer derived from the tripartite complex Patj/Pals1/Mals2. The heterotrimer consists of two cognate pairs of heterodimeric L27 domains with similar conformations. Structural analysis and biochemical data further show that the dimers assemble mutually independently. Additionally, such mutually independent assembly of the two heterodimers can be observed in another tripartite complex, Disks large homolog 1 (DLG1)/calcium-calmodulin-dependent serine protein kinase (CASK)/Mals2. Our results reveal a novel mechanism for tandem L27 domain-mediated, supramolecular complex assembly with a mutually independent mode.
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Nankai University, 94 Weijin Road, Tianjin 300071, China.
authors.forename: Jinxiu
authors.initials: J
authors.lastname: Zhang
authors.forename: Xue
authors.initials: X
authors.lastname: Yang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.forename: Hao
authors.initials: H
authors.lastname: Zhou
authors.forename: Xingqiao
authors.initials: X
authors.lastname: Xie
authors.forename: Yuequan
authors.initials: Y
authors.lastname: Shen
authors.forename: Jiafu
authors.initials: J
authors.lastname: Long
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism; D016764:Cell Polarity; D018360:Crystallography, X-Ray; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D009703:Nucleoside-Phosphate Kinase / Q000737:chemistry* / Q000378:metabolism; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D013379:Substrate Specificity
chemical_list: D002352:Carrier Proteins; C485432:Lin7b protein, mouse; D008565:Membrane Proteins; C575001:Patj protein, rat; D009703:Nucleoside-Phosphate Kinase; C501307:MPP5 protein, human