Structural features of the human salivary mucin, MUC7.
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 (approximately 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.
Gururaja
T L
TL
Department of Oral Biology and Research Center in Oral Biology, School of Dental Medicine, State University of New York at Buffalo, 14214, USA.
Ramasubbu
N
N
Venugopalan
P
P
Reddy
M S
MS
Ramalingam
K
K
Levine
M J
MJ
D000595:Amino Acid Sequence; D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D006031:Glycosylation; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009077:Mucins / Q000737:chemistry*; D011392:Proline / Q000737:chemistry; D011487:Protein Conformation; D021382:Protein Sorting Signals / Q000737:chemistry; D012471:Salivary Proteins and Peptides / Q000737:chemistry*
C083238:MUC7 protein, human; D009077:Mucins; D021382:Protein Sorting Signals; D012471:Salivary Proteins and Peptides; D011392:Proline