8CD3

Crystal structure of human Scribble PDZ1 domain in complex with human TMIGD1

Summary for 8CD3

• Entry DOI: 10.2210/pdb8cd3/pdb
• Descriptor: Protein scribble homolog, Transmembrane and immunoglobulin domain-containing protein 1 (3 entities in total)
• Functional Keywords: pdz domain, cell polarity, scribble, transmembrane protein, protein binding
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 11747.20

Authors

Maddumage, J.C.,Kvansakul, M. (deposition date: 2023-01-30, release date: 2024-01-31)

Primary citation

Thuring, E.M.,Hartmann, C.,Maddumage, J.C.,Javorsky, A.,Michels, B.E.,Gerke, V.,Banks, L.,Humbert, P.O.,Kvansakul, M.,Ebnet, K.
Membrane recruitment of the polarity protein Scribble by the cell adhesion receptor TMIGD1.
Commun Biol, 6:702-702, 2023

PubMed Abstract: Scribble (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.

PubMed: 37430142
DOI: 10.1038/s42003-023-05088-3

Experimental method

X-RAY DIFFRACTION (1.9 Å)