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Structural features of the human salivary mucin, MUC7 | SpringerLink

Glycoconjugate Journal

, Volume 15, Issue 5, pp 457–467 | Cite as

Structural features of the human salivary mucin, MUC7

  • Tarikere L Gururaja
  • Narayanan Ramasubbu
  • Paloth Venugopalan
  • Molakala S Reddy
  • Kalaiyarasi Ramalingam
  • Michael J Levine

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.

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 

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Copyright information

© Chapman and Hall 1998

Authors and Affiliations

  • Tarikere L Gururaja
    • 1
  • Narayanan Ramasubbu
    • 1
  • Paloth Venugopalan
    • 1
  • Molakala S Reddy
    • 1
  • Kalaiyarasi Ramalingam
    • 1
  • Michael J Levine
    • 1
  1. 1.Department of Oral Biology and Research Center in Oral Biology, 109 Foster Hall, School of Dental MedicineState University of New York at BuffaloBuffaloUSA

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