2ACM

Solution structure of the SEA domain of human mucin 1 (MUC1)

Summary for 2ACM

• Entry DOI: 10.2210/pdb2acm/pdb
• Descriptor: Mucin-1 (2 entities in total)
• Functional Keywords: auto-catalytic proteolysis, structural protein
• Biological source: Homo sapiens (human); More
• Cellular location: Apical cell membrane; Single-pass type I membrane protein. Isoform 5: Secreted. Isoform 7: Secreted. Isoform 9: Secreted. Mucin-1 subunit beta: Cell membrane: Q16615 Q16615
• Total number of polymer chains: 2
• Total formula weight: 13879.25

Authors

Macao, B.,Johansson, D.G.A.,Hansson, G.C.,Hard, T. (deposition date: 2005-07-19, release date: 2006-01-17, Last modification date: 2024-05-29)

Primary citation

Macao, B.,Johansson, D.G.A.,Hansson, G.C.,Hard, T.
Autoproteolysis coupled to protein folding in the SEA domain of the membrane-bound MUC1 mucin
Nat.Struct.Mol.Biol., 13:71-76, 2006

PubMed Abstract: The single cell layer of the lungs and the gastrointestinal tract is protected by the mucus formed by large glycoproteins called mucins. Transmembrane mucins typically contain 110-residue SEA domains located next to the membrane. These domains undergo post-translational cleavage between glycine and serine in a characteristic GSVVV sequence, but the two peptides remain tightly associated. We show that the SEA domain of the human MUC1 transmembrane mucin undergoes a novel type of autoproteolysis, which is catalyzed by conformational stress and the conserved serine hydroxyl. We propose that self-cleaving SEA domains have evolved to dissociate as a result of mechanical rather than chemical stress at the apical cell membrane and that this protects epithelial cells from rupture. We further suggest that the cell can register mechanical shear at the mucosal surface if the dissociation is signaled via loss of a SEA-binding protein.

PubMed: 16369486
DOI: 10.1038/nsmb1035

Experimental method

SOLUTION NMR