4mzv
From Proteopedia
Crystal structure of extracellular part of human EpCAM
Structural highlights
Disease[EPCAM_HUMAN] Intestinal epithelial dysplasia;Hereditary nonpolyposis colon cancer. The disease is caused by mutations affecting the gene represented in this entry.[1] The disease is caused by mutations affecting the gene represented in this entry. HNPCC8 results from heterozygous deletion of 3-prime exons of EPCAM and intergenic regions directly upstream of MSH2, resulting in transcriptional read-through and epigenetic silencing of MSH2 in tissues expressing EPCAM.[2] Function[EPCAM_HUMAN] May act as a physical homophilic interaction molecule between intestinal epithelial cells (IECs) and intraepithelial lymphocytes (IELs) at the mucosal epithelium for providing immunological barrier as a first line of defense against mucosal infection. Plays a role in embryonic stem cells proliferation and differentiation. Up-regulates the expression of FABP5, MYC and cyclins A and E.[3] [4] [5] [6] Publication Abstract from PubMedEpCAM (epithelial cell adhesion molecule), a stem and carcinoma cell marker, is a cell surface protein involved in homotypic cell-cell adhesion via intercellular oligomerization and proliferative signalling via proteolytic cleavage. Despite its use as a diagnostic marker and being a drug target, structural details of this conserved vertebrate-exclusive protein remain unknown. Here we present the crystal structure of a heart-shaped dimer of the extracellular part of human EpCAM. The structure represents a cis-dimer that would form at cell surfaces and may provide the necessary structural foundation for the proposed EpCAM intercellular trans-tetramerization mediated by a membrane-distal region. By combining biochemical, biological and structural data on EpCAM, we show how proteolytic processing at various sites could influence structural integrity, oligomeric state and associated functionality of the molecule. We also describe the epitopes of this therapeutically important protein and explain the antigenicity of its regions. Crystal structure and its bearing towards an understanding of key biological functions of EpCAM.,Pavsic M, Guncar G, Djinovic-Carugo K, Lenarcic B Nat Commun. 2014 Aug 28;5:4764. doi: 10.1038/ncomms5764. PMID:25163760[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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