Abstract
Human salivary mucin (MUC7) is characterized by a single polypeptide chain of 357 aa. Detailed analysis of the derived MUC7 peptide sequence reveals five distinct regions or domains: (1) an N-terminal basic, histatin-like domain which has a leucine-zipper segment, (2) a moderately glycosylated domain, (3) six heavily glycosylated tandem repeats each consisting of 23 aa, (4) another heavily glycosylated MUC1- and MUC2-like domain, and (5) a C-terminal leucine-zipper segment. Chemical analysis and semi-empirical prediction algorithms for O-glycosylation suggested that 86/105 (83%) Ser/Thr residues were O-glycosylated with the majority located in the tandem repeats. The high (∼25%) proline content of MUC7 including 19 diproline segments suggested the presence of polyproline type structures. CD studies of natural and synthetic diproline-rich peptides and glycopeptides indicated that polyproline type structures do play a significant role in the conformational dynamics of MUC7. In addition, crystal structure analysis of a synthetic diproline segment (Boc-Ala-Pro-OBzl) revealed a polyproline type II extended structure. Collectively, the data indicate that the polyproline type II structure, dispersed throughout the tandem repeats, may impart a stiffening of the backbone and could act in consort with the glycosylated segments to keep MUC7 in a semi-rigid, rod shaped conformation resembling a ‘bottle-brush’ model.
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Gururaja, T.L., Ramasubbu, N., Venugopalan, P. et al. Structural features of the human salivary mucin, MUC7. Glycoconj J 15, 457–467 (1998). https://doi.org/10.1023/A:1006978818555
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DOI: https://doi.org/10.1023/A:1006978818555
- Salivary mucin (MUC7)
- O-glycosylation
- APP segments
- tandem repeat
- (glyco)peptide synthesis
- crystallization
- X-ray diffraction
- poly-L-proline type conformation
- aa, amino acid
- MUC7, human salivary mucin
- APP, Ala-Pro-Pro, Boc-Ala-Pro-Pro-OBzl
- Boc, Nα-t-butyloxycarbonyl
- Bzl, benzyl
- CD, circular dichroism
- e.s.ds, estimated standard deviations
- Fmoc, Nα-fluorenylmethoxycarbonyl
- Fuc, fucose
- Gal, galactose
- GalNAc, N-acetylgalactosamine
- MALDI, matrix assisted laser desorptionionization
- PPI, poly-L-proline type I conformation
- PPII, poly-L-proline type II conformation
- NeuAc, sialic acid
- SPPS, solid-phase peptide synthesis
- SSCP, secondary structure content prediction