Presence and structure-activity relationship of intrinsically disordered regions across mucins.
glycoprotein
intrinsically disordered protein
protein structure
protein-protein interaction
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
received:
26
07
2019
revised:
18
11
2019
accepted:
05
12
2019
pubmed:
8
1
2020
medline:
29
9
2020
entrez:
8
1
2020
Statut:
ppublish
Résumé
Many members of the mucin family are evolutionarily conserved and are often aberrantly expressed and glycosylated in various benign and malignant pathologies leading to tumor invasion, metastasis, and immune evasion. The large size and extensive glycosylation present challenges to study the mucin structure using traditional methods, including crystallography. We offer the hypothesis that the functional versatility of mucins may be attributed to the presence of intrinsically disordered regions (IDRs) that provide dynamism and flexibility and that the IDRs offer potential therapeutic targets. Herein, we examined the links between the mucin structure and function based on IDRs, posttranslational modifications (PTMs), and potential impact on their interactome. Using sequence-based bioinformatics tools, we observed that mucins are predicted to be moderately (20%-40%) to highly (>40%) disordered and many conserved mucin domains could be disordered. Phosphorylation sites overlap with IDRs throughout the mucin sequences. Additionally, the majority of predicted O- and N- glycosylation sites in the tandem repeat regions occur within IDRs and these IDRs contain a large number of functional motifs, that is, molecular recognition features (MoRFs), which directly influence protein-protein interactions (PPIs). This investigation provides a novel perspective and offers an insight into the complexity and dynamic nature of mucins.
Identifiants
pubmed: 31908009
doi: 10.1096/fj.201901898RR
pmc: PMC7018569
mid: NIHMS1063583
doi:
Substances chimiques
Mucins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1939-1957Subventions
Organisme : NCI NIH HHS
ID : U01 CA200466
Pays : United States
Organisme : NCI NIH HHS
ID : R44 CA224619
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA195586
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA210240
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA183459
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA210637
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA217798
Pays : United States
Informations de copyright
© 2020 Federation of American Societies for Experimental Biology.
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