Structure and function of glycosylated tandem repeats from Candida albicans als adhesins

Aaron T. Frank, Caleen B. Ramsook, Henry N. Otoo, Cho Tan, Gregory Soybelman, Jason M. Rauceo, Nand K. Gaur, Stephen A. Klotz, Peter N. Lipke

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36 Scopus citations

Abstract

Tandem repeat (TR) regions are common in yeast adhesins, but their structures are unknown, and their activities are poorly understood. TR regions in Candida albicans Als proteins are conserved glycosylated 36-residue sequences with cell-cell aggregation activity (J. M. Rauceo, R. De Armond, H. Otoo, P. C. Kahn, S. A. Klotz, N. K. Gaur, and P. N. Lipke, Eukaryot. Cell 5:1664-1673, 2006). Ab initio modeling with either Rosetta or LINUS generated consistent structures of three-stranded antiparallel β-sheet domains, whereas randomly shuffled sequences with the same composition generated various structures with consistently higher energies. O-and N-glycosylation patterns showed that each TR domain had exposed hydrophobic surfaces surrounded by glycosylation sites. These structures are consistent with domain dimensions and stability measurements by atomic force microscopy (D. Alsteen, V. Dupres, S. A. Klotz, N. K. Gaur, P. N. Lipke, and Y. F. Dufrene, ACS Nano 3:1677-1682, 2009) and with circular dichroism determination of secondary structure and thermal stability. Functional assays showed that the hydrophobic surfaces of TR domains supported binding to polystyrene surfaces and other TR domains, leading to nonsaturable homophilic binding. The domain structures are like "classic" subunit interaction surfaces and can explain previously observed patterns of promiscuous interactions between TR domains in any Als proteins or between TR domains and surfaces of other proteins. Together, the modeling techniques and the supporting data lead to an approach that relates structure and function in many kinds of repeat domains in fungal adhesins.

Original languageEnglish (US)
Pages (from-to)405-414
Number of pages10
JournalEukaryotic Cell
Volume9
Issue number3
DOIs
StatePublished - Mar 1 2010

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

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    Frank, A. T., Ramsook, C. B., Otoo, H. N., Tan, C., Soybelman, G., Rauceo, J. M., Gaur, N. K., Klotz, S. A., & Lipke, P. N. (2010). Structure and function of glycosylated tandem repeats from Candida albicans als adhesins. Eukaryotic Cell, 9(3), 405-414. https://doi.org/10.1128/EC.00235-09