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The reduction-insensitive bonds of the MUC2 mucin are isopeptide bonds.

Författare och institution:
Christian V Recktenwald (Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi); Gunnar C. Hansson (Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi)
Publicerad i:
The Journal of biological chemistry, 291 ( 26 ) s. 13580-13590
ISSN:
1083-351X
Publikationstyp:
Artikel, refereegranskad vetenskaplig
Publiceringsår:
2016
Språk:
engelska
Fulltextlänk:
Sammanfattning (abstract):
The main structural component of the mucus in the gastrointestinal tract is the MUC2 mucin. It forms large networks that in colon builds the loose outer mucus layer that provides the habitat for the commensal flora and the inner mucus layer that protects the epithelial cells by being impenetrable to bacteria. The epithelial cells in mice lacking MUC2 are not adequately protected from bacteria, resulting in inflammation and the development of colon cancer as found in human ulcerative colitis. Correct processing of the MUC2 mucin is the basis for the building of these protective networks. During the biosynthesis of the MUC2 mucin posttranslational modifications are formed resulting in reduction-insensitive bonds between MUC2 monomers. By the use of γ-glutamyl-transpeptidase and isopeptidase activity in leech saliva we could show that the molecular nature of these reduction-insensitive bonds are isopeptide bonds formed between side-chains of lysine and glutamine. Transglutaminase 2 (TGM2) has an affinity to the MUC2 CysD2 domain in the nanomolar range and can catalyze its cross-linking. By using mass spectrometry, we identified MUC2 residues involved in this cross-linking. This shows for the first time that transamidation is not only stabilizing the skin and the fibrin-clot, but is also important for the correct intracellular processing of MUC2 to generate protective mucus.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
MEDICIN OCH HÄLSOVETENSKAP ->
Medicinska grundvetenskaper
MEDICIN OCH HÄLSOVETENSKAP ->
Medicinska grundvetenskaper ->
Annan medicinsk grundvetenskap ->
Kemi
Postens nummer:
236569
Posten skapad:
2016-05-16 10:03
Posten ändrad:
2016-08-12 13:46

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