Macao Bertil, Johansson Denny G A, Hansson Gunnar C, Härd Torleif
Department of Medical Biochemistry, Göteborg University, Box 440, SE-405 30 Göteborg, Sweden.
Nat Struct Mol Biol. 2006 Jan;13(1):71-6. doi: 10.1038/nsmb1035. Epub 2005 Dec 20.
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.
肺和胃肠道的单细胞层由称为粘蛋白的大型糖蛋白形成的粘液保护。跨膜粘蛋白通常在膜附近含有110个残基的SEA结构域。这些结构域在特征性的GSVVV序列中的甘氨酸和丝氨酸之间进行翻译后切割，但两个肽段仍紧密相连。我们发现人MUC1跨膜粘蛋白的SEA结构域经历了一种新型的自催化裂解，这是由构象应力和保守的丝氨酸羟基催化的。我们提出，自切割SEA结构域由于顶端细胞膜上的机械而非化学应力而进化为解离，这保护上皮细胞免于破裂。我们进一步表明，如果通过SEA结合蛋白的丢失发出解离信号，细胞可以感知粘膜表面的机械剪切力。
