Current View on EpCAM Structural Biology
Open Access
- 30 May 2020
- Vol. 9 (6), 1361
- https://doi.org/10.3390/cells9061361
Abstract
EpCAM, a carcinoma cell-surface marker protein and a therapeutic target, has been primarily addressed as a cell adhesion molecule. With regard to recent discoveries of its role in signaling with implications in cell proliferation and differentiation, and findings contradicting a direct role in mediating adhesion contacts, we provide a comprehensive and updated overview on the available structural data on EpCAM and interpret it in the light of recent reports on its function. First, we describe the structure of extracellular part of EpCAM, both as a subunit and part of a cis-dimer which, according to several experimental observations, represents a biologically relevant oligomeric state. Next, we provide a thorough evaluation of reports on EpCAM as a homophilic cell adhesion molecule with a structure-based explanation why direct EpCAM participation in cell–cell contacts is highly unlikely. Finally, we review the signaling aspect of EpCAM with focus on accessibility of signaling-associated cleavage sites.Keywords
Funding Information
- Javna Agencija za Raziskovalno Dejavnost RS (J1-2017, J1-7119, P1-0140, P1-0207)
This publication has 100 references indexed in Scilit:
- The many faces and functions of β-cateninThe EMBO Journal, 2012
- Putting the Pieces Together: Integrative Modeling Platform Software for Structure Determination of Macromolecular AssembliesPLoS Biology, 2012
- Biochemical and Structural Characterization of β-Catenin Interactions with Nonphosphorylated and CK2-Phosphorylated Lef-1Journal of Molecular Biology, 2011
- The tumor-associated EpCAM regulates morphogenetic movements through intracellular signalingThe Journal of cell biology, 2010
- Structure prediction for CASP8 with all‐atom refinement using RosettaProteins-Structure Function and Bioinformatics, 2009
- Identification of EpCAM as the Gene for Congenital Tufting EnteropathyGastroenterology, 2008
- Assembly reflects evolution of protein complexesNature, 2008
- Secondary-structure matching (SSM), a new tool for fast protein structure alignment in three dimensionsActa Crystallographica Section D-Biological Crystallography, 2004
- UCSF Chimera?A visualization system for exploratory research and analysisJournal of Computational Chemistry, 2004
- Crystal Structure of the Complex of Human Epidermal Growth Factor and Receptor Extracellular DomainsCell, 2002