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8cd3
From Proteopedia
Crystal structure of human Scribble PDZ1 domain in complex with human TMIGD1
Structural highlights
DiseaseSCRIB_HUMAN The disease is caused by mutations affecting the gene represented in this entry. FunctionSCRIB_HUMAN Scaffold protein involved in different aspects of polarized cells differentiation regulating epithelial and neuronal morphogenesis. Most probably functions in the establishment of apico-basal cell polarity. May function in cell proliferation regulating progression from G1 to S phase and as a positive regulator of apoptosis for instance during acinar morphogenesis of the mammary epithelium. May also function in cell migration and adhesion and hence regulate cell invasion through MAPK signaling. May play a role in exocytosis and in the targeting synaptic vesicles to synapses. Functions as an activator of Rac GTPase activity.[1] [2] [3] [4] [5] [6] [7] Publication Abstract from PubMedScribble (Scrib) is a multidomain polarity protein and member of the leucine-rich repeat and PDZ domain (LAP) protein family. A loss of Scrib expression is associated with disturbed apical-basal polarity and tumor formation. The tumor-suppressive activity of Scrib correlates with its membrane localization. Despite the identification of numerous Scrib-interacting proteins, the mechanisms regulating its membrane recruitment are not fully understood. Here, we identify the cell adhesion receptor TMIGD1 as a membrane anchor of Scrib. TMIGD1 directly interacts with Scrib through a PDZ domain-mediated interaction and recruits Scrib to the lateral membrane domain in epithelial cells. We characterize the association of TMIGD1 with each Scrib PDZ domain and describe the crystal structure of the TMIGD1 C-terminal peptide complexed with PDZ domain 1 of Scrib. Our findings describe a mechanism of Scrib membrane localization and contribute to the understanding of the tumor-suppressive activity of Scrib. Membrane recruitment of the polarity protein Scribble by the cell adhesion receptor TMIGD1.,Thuring EM, Hartmann C, Maddumage JC, Javorsky A, Michels BE, Gerke V, Banks L, Humbert PO, Kvansakul M, Ebnet K Commun Biol. 2023 Jul 10;6(1):702. doi: 10.1038/s42003-023-05088-3. PMID:37430142[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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