Our understanding of the origins of the physical and biochemical properties of mucous glycoproteins is incomplete and not with out controversy. Recent molecular biological and biophysical studies revealing the architecture and solution structure and dynamics of a series of salivary mucins, invaluable toward resolving many of these questions, are discussed. Mucins are very large, structurally heterogeneous, and highly expanded molecules with the carbohydrate playing a key role in maintaining the extended mucin conformation.
References
1.
Bhavanandan, V.P. and J.D. Hegarty: Identification of the Mucin Core Protein by Cell-free Translation of Messenger RNA from Bovine Submaxillary Glands. J. Biol. Chem. 262:5913-5917 (1987).
2.
Bhargava, A.K., J.T. Woitach, E.A. Davidson, and V.P. Bhavanandan: Cloning and cDNA Sequence of a Bovine Submaxillary Gland Mucin-like Protein Containing Two Distinct Domains. Proc. Natl. Acad. Sci. U.S.A.87:6798-6802 (1990 ).
3.
Bush, C.A., Z.Y. Yan, and B.N.N. Rao: Conformational Energy Calculations and Proton Nuclear Overhauser Enhancements Reveal a Unique Conformation for Blood Group A Oligosaccharides. J. Am. Chem. Soc. 108:6168-6173 (1986 ).
4.
Butenhof, K.J. and T.A. Gerken: Structure and Dynamics of Mucin-like Glycopeptides. Examination of Peptide Chain Expansion and Peptide-Carbohydrate Interactions by Stochastic Dynamics Simulations. Biochemistry32:650-2663.
5.
Carlstedt, I., J.K. Sheehan, A.P. Corfield, and J.T. Gallagher: Mucous Glycoproteins: A Gel of a Problem. Essays Biochem. 20:40-76 (1985).
6.
Eckhardt, A.E., C.S. Timpte, J.L. Abernethy, A. Toumedje, W.C. Johnson, and R.L. Hill: Structural Properties of Porcine Submaxillary Glands Apo Mucin. J. Biol. Chem.262:11339-11344 (1987).
7.
Eckhardt, A.E., C.S. Timpte, J.L. Abemethy, Y. Zhao, and R.L. Hill: Porcine Submaxillary Mucin Contains a Cystine-rich, Carboxyl-terminal Domain in Addition to a Highly Repetitive, Glycosylated Domain. J. Biol. Chem. 266:9678-9686 (1991).
8.
Flippen, J.L.: The Crystal Structure of β-D-N-Acetylneuraminic Acid Dihydrate (Sialic Acid), C11H19NO92H2O. Acta Cryst. B29:1881-1886 (1993).
9.
Gendler, S.J., C.A. Lancaster, J. Taylor-Papadimitriou, T. Duhig, N. Peat, J. Burchell, L. Pemberton, E.N. Lalani, and D. Wilson: Molecular Cloning and Expression of Human Tumor-associated Polymorphic Epithelial Mucin. J. Biol. Chem. 265:15286-15293 (1990 ).
10.
Gerken, T.A.: The Solution Structure of Mucous Glycoproteins: Proton NMR Studies of Native and Modified Ovine Submaxillary Mucin. Arch. Biochem. Biophys. 247:239-253 (1986).
11.
Gerken, T.A., K.J. Butenhof, and R.L. Shogren: Effects of Glycosylation on the Conformation and Dynamics of O-linked Glycoproteins: Carbon-13 NMR Studies of Ovine Submaxillary Mucin. Biochemistry28:5536-5543 (1989).
12.
Gerken, T.A. and D.G. Dearborn: Carbon-13 NMR Studies of Native and Modified Ovine Submaxillary Mucin. Biochemistry23:1485-1497 (1984).
13.
Gerken, T.A., R. Gupta, and N. Jentoft: A Novel Approach for Chemically Deglycosylating O-linked Glycoproteins. The Deglycosylation of Submaxillary and Respiratory Mucins. Biochemistry31:639-648 (1992).
14.
Gerken, T.A. and N. Jentoft: Structure and Dynamics of Porcine Submaxillary Mucin as Determined by Natural Abundance Carbon-13 NMR Spectroscopy. Biochemistry26:4689-4699 (1987).
15.
Gum, J.R., J.C. Byrd, J.W. Hicks, N.W. Toribarat, D.T.A. Lamport, and Y.S. Kim: Molecular Cloning of Human Intestinal Mucin cDNAs: Sequence Analysis and Evidence for Genetic Polymorphism. J. Biol. Chem. 264:6480-6487 (1989).
16.
Gum, J.R., J.W. Hicks, D.M. Swallow, R.L. Lagaec, J.C. Byrd, D.T.A. Lamport, B. Siddiki, and Y.S. Kim: Molecular Cloning of cDNAs Derived from a Novel Human Intestinal Mucin Gene. Biochem. Biophys. Res. Commun. 171:407-415 (1990).
17.
Gupta R. and N. Jentoft: Subunit Structure of Porcine Submaxillary Mucin. Biochemistry28:6114-6121 (1989).
18.
Gupta, R., N. Jentoft, A.M. Jamieson, and J. Blackwell: Structural Analysis of Purified Human Tracheobronchial Mucins. Biopolymers29:347-355 (1990).
19.
Harding, S.E.: The Macrostructure of Mucus Glycoproteins in Solution. Adv. Carbohydr. Chem. Biochem. 47:345-381 (1989).
20.
Hill, H.D., J.A. Reynolds, and R.L. Hill: Purification, Composition, Molecular Weight, and Subunit Structure of Ovine Submaxillary Mucin. J. Biol. Chem. 252:3791-3798 (1977).
21.
Jany, B.H., M.W. Gallup, P.S. Yan, J.R. Gum, Y.S. Kim, and C.B. Basbaum: Human Bronchus and Intestine Express the Same Mucin Gene. J. Clin. Invest. 87:77-82 (1991).
22.
Jorgenson, W.J. and J. Tirado-Rives: The OPLS Potential Functions for Proteins. Energy Minimizations for Crystals of Cyclic Peptides and Crambin. J. Am. Chem. Soc. 110:1657-1671 (1988 ).
23.
Kooijman, H., L.M.J. Kroon-Batenburg, and J. Kroon: Structure of α-D-N-Acetyl-1-O-Methylneuraminic Acid Methyl Ester. Acta Cryst. C46:407-410 (1990).
24.
Lan, M.S., M.A. Hollingsworth, and R.S. Metzgar: Polypeptide Core of a Human Pancreatic Tumor Mucin Antigen. Cancer Res. 50:2997-3001 (1990).
25.
Marianne, T., J.M. Perini, J.J. Lafitte, N. Houdret, F.R. Pruvot, G. Lamblin, H.S. Slayter and P. Roussel: Peptides of Human Bronchial Mucus Glycoproteins: Size Determination by Electron Microscopy and by Biosynthetic Experiments. Biochem. J. 248:189-195 (1987).
26.
Porchet, N., N. Van Cong, J. Dufosse, J.P. Audie, V. Guvonnet-Duperat, M.S. Gross, C. Denis, P. Degand, A. Bernheim, and J.P. Aubert: Molecular Cloning and Chromosomal Location of a Novel Human Tracheobronchial Mucin cDNA Containing Tandemly Repeated Sequences of 48 Base Pairs. Biochem. Biophys. Res. Commun.175:414-422 (1991).
27.
Ringler, N., R. Selvakumar, H.D. Woodward, I.M. Simet, V.P. Bhavanandan, and E.A. Davidson: Protein Components of Human Tracheobronchial Mucin: Partial Characterization of a Closely Associated 65-kilodalton Protein. Biochemistry27:8056-8063 (1988).
28.
Roberton, A.M., M. Mantle, R.E. Fahim, R.D. Specian, A. Bennick, S. Kawagishi, P. Sherman, and F. Forstner: The Putative 'Link' Glycopeptide Associated with Mucus Glyoproteins, Composition and Properties of Preparations from the Gastrointestinal Tracts of Several Mammals. Biochem. J. 261:637-647 (1989).
29.
Sellers, L.A., A. Allen, E.R. Morris, and S.B. Ross-Murphy: Mucus Glycoprotein Gels. Role of Glycoprotein Polymeric Structure and Carbohydrate Side-chains in Gel-formation. Carbohydr. Res. 178:93-110 (1988).
30.
Shankar, V., B. Nariruddin, S.R. De La Rocha, and G.P. Sachdev: Evidence of Hydrophobic Domains in Human Respiratory Mucins. Effect of Sodium Chloride on Hydrophobic Binding Properties. Biochemistry29:5856-5864 (1990).
31.
Sheehan, J.K., K. Oates, and I. Carlstedt: Electron Microscopy of Cervical, Gastric and Bronchial Mucus Glycoproteins. Biochem. J. 239:147-153 (1986).
32.
Sheehan, J.K., D.J. Thornton, M. Somerville, and I. Carlstedt: Mucin Structure. Am. Rev. Respir. Dis. 144:S4-S9 (1991).
33.
Shogren, R., T.A. Gerken, and N. Jentoft: Role of Glycosylation on the Conformation and Chain Dimensions of O-linked Glycoproteins: Light-scattering Studies of Ovine Submaxillary Mucin. Biochemistry28:5525-5536 (1989).
34.
Shogren, R.L., A.M. Jamieson, J. Blackwell, and N. Jentoft: Conformation of Mucous Glycoproteins in Aqueous Solvents. Biopolymers25:1505-1517 (1986).
35.
Shogren, R.L., N. Jentoft, T.A. Gerken, A.M. Jamieson, and J. Blackwell: Light-scattering Studies of Fractionated Ovine Submaxillary Mucins. Carbohydr. Res. 160:317-327 (1987).
36.
Soby, L.M., A. Jamieson, J. Blackwell, and N. Jentoft: Viscoelastic Properties of Solutions of Ovine Submaxillary Mucin. Biopolymers29:1359-1366 (1990).
37.
Still, W.C., A. Tempczyk, R.C. Hawley, and T. Hendrickson: Semianalytical Treatment of Solvation for Molecular Mechanics and Dynamics. J. Am. Chem. Soc. 112:6127-6129 (1990 ).
38.
Strous, G.J. and J. Dekker: Mucin-type Glycoproteins. Crit. Rev. Biochem. Mol. Biol. 27:57-92 (1992).
39.
Yan, Z.Y. and C.A. Bush: Molecular Dynamics Simulations and the Conformational Mobility of Blood Group Oligosaccharides. Biopolymers29:799-811 (1990).
