Autoproteolysis coupled to protein folding in the SEA domain of the membrane-bound MUC1 mucin.

• 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.

Nyckelord

Amino Acid Sequence

Animals

CA-15-3 Antigen

chemistry

genetics

metabolism

Catalysis

Cell Membrane

metabolism

Dimerization

Humans

Models

Molecular

Molecular Sequence Data

Mutation

genetics

Nuclear Magnetic Resonance

Biomolecular

Protein Binding

Protein Denaturation

Protein Folding

Protein Structure

Quaternary

Protein Structure

Tertiary

Sequence Alignment

Temperature

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)