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8S03

NMR solution structure of the CysD2 domain of MUC2

Summary for 8S03
Entry DOI10.2210/pdb8s03/pdb
NMR InformationBMRB: 34899
DescriptorMucin-2, CALCIUM ION (2 entities in total)
Functional Keywordscolon, transglutaminase, isopeptide bond, structural protein
Biological sourceHomo sapiens (human)
Total number of polymer chains1
Total formula weight15261.20
Authors
Recktenwald, C.,Karlsson, B.G.,Garcia-Bonnete, M.-J.,Katona, G.,Jensen, M.,Lymer, R.,Baeckstroem, M.,Johansson, M.E.V.,Hansson, G.C.,Trillo-Muyo, S. (deposition date: 2024-02-13, release date: 2024-04-17, Last modification date: 2024-11-06)
Primary citationRecktenwald, C.V.,Karlsson, G.,Garcia-Bonete, M.J.,Katona, G.,Jensen, M.,Lymer, R.,Backstrom, M.,Johansson, M.E.V.,Hansson, G.C.,Trillo-Muyo, S.
The structure of the second CysD domain of MUC2 and role in mucin organization by transglutaminase-based cross-linking.
Cell Rep, 43:114207-114207, 2024
Cited by
PubMed Abstract: The 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.
PubMed: 38733585
DOI: 10.1016/j.celrep.2024.114207
PDB entries with the same primary citation
Experimental method
SOLUTION NMR
Structure validation

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