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Journal of Dental Research
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Molecular Mapping of Statherin- and Histatin-binding Domains in Human Salivary Mucin MG1 (MUC5B) by the Yeast Two-hybrid System

I. lontcheva

Department of Periodontology and Oral Biology, Goldman School of Dental Medicine, Boston

F.G. Oppenheim

Department of Biochemistry, Department of Periodontology and Oral Biology, Goldman School of Dental Medicine, Boston

G.D. Offner

Medicine, Boston University School of Medicine, 80 East Concord Street, Boston, MA 02118, USA

R.F. Troxler

Department of Biochemistry, Department of Periodontology and Oral Biology, Goldman School of Dental Medicine, Boston

MG1 is a high-molecular-weight mucin secreted by mucous acinar cells in human submandibular and sublingual glands. We have recently shown that the tracheobronchial mucin MUC5B is a major component of MG1. MUC5B is organized into cysteine-rich N- and C-terminal regions that flank a central tandem-repeat region containing cysteine-rich subdomains and imperfect 29-residue tandem repeats. In earlier work, we have shown that this mucin selectively forms heterotypic complexes with amylase, proline-rich proteins, statherin, and histatins in salivary secretions, and the aim of this study was to identify specific binding domains within MUC5B using the yeast two-hybrid system. Interactions of cysteine-rich domains in the tandem-repeat region (Cysl-Cys4) and C-terminal region (Cys8a, Cys8b, Cys8c) of MUC5B with statherin and histatins were investigated. These studies indicated that histatin 1 selectively bound to Cysl and Cys2, whereas statherin and histatin 1, 3, and 5 selectively bound to Cys8a. Analysis of the primary sequences of the identified binding domains suggests that these domains most probably can fold into globular-like structures in the native mucin. A ProDom blast search revealed that sequences in Cys1, Cys2, and Cys8a exhibit similarity to domains in evolutionarily diverse extracellular proteins known to participate in a wide variety of protein-protein interactions.

Key Words: heterotypic complexes • salivary proteins • protein-protein interaction.

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Journal of Dental Research, Vol. 79, No. 2, 732-739 (2000)
DOI: 10.1177/00220345000790020601
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