8s03
NMR solution structure of the CysD2 domain of MUC2
Structural highlights
FunctionMUC2_HUMAN Coats the epithelia of the intestines, airways, and other mucus membrane-containing organs. Thought to provide a protective, lubricating barrier against particles and infectious agents at mucosal surfaces. Major constituent of both the inner and outer mucus layers of the colon and may play a role in excluding bacteria from the inner mucus layer.[1] Publication Abstract from PubMedThe MUC2 mucin protects the colonic epithelium by a two-layered mucus with an inner attached bacteria-free layer and an outer layer harboring commensal bacteria. CysD domains are 100 amino-acid-long sequences containing 10 cysteines that separate highly O-glycosylated proline, threonine, serine (PTS) regions in mucins. The structure of the second CysD, CysD2, of MUC2 is now solved by nuclear magnetic resonance. CysD2 shows a stable stalk region predicted to be partly covered by adjacent O-glycans attached to neighboring PTS sequences, whereas the CysD2 tip with three flexible loops is suggested to be well exposed. It shows transient dimer interactions at acidic pH, weakened at physiological pH. This transient interaction can be stabilized in vitro and in vivo by transglutaminase 3-catalyzed isopeptide bonds, preferring a specific glutamine residue on one flexible loop. This covalent dimer is modeled suggesting that CysD domains act as connecting hubs for covalent stabilization of mucins to form a protective mucus. The structure of the second CysD domain of MUC2 and role in mucin organization by transglutaminase-based cross-linking.,Recktenwald CV, Karlsson G, Garcia-Bonete MJ, Katona G, Jensen M, Lymer R, Backstrom M, Johansson MEV, Hansson GC, Trillo-Muyo S Cell Rep. 2024 May 28;43(5):114207. doi: 10.1016/j.celrep.2024.114207. Epub 2024 , May 9. PMID:38733585[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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