Cited by 63Fungal and yeast genetics researchGlycosylation and Glycoproteins ResearchAntifungal resistance and susceptibility

Structure and Function of Glycosylated Tandem Repeats from Candida albicans Als Adhesins

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Frank, Aaron T., Ramsook, Caleen B., Otoo, Henry N., Tan, Cho, Soybelman, Gregory, Rauceo, Jason M., Gaur, Nand K., Klotz, Stephen A. +1 more·2010·Eukaryotic Cell

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.

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Crossref · 10.1128/ec.00235-09

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  • Previous studies show that variations in tandem repeat copy numbers within fungal adhesin proteins can affect their surface hydrophobicity, cell surface display, and protein shedding, ultimately influencing their functions.

    “This agrees with previous studies showing that variations in tandem repeat copy numbers within fungal adhesin proteins can affect their surface hydrophobicity, cell surface display, and protein shedding, ultimately influencing their functions52,53.”

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Authors
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.
Affiliations
  • University of Michigan (US)
  • City University of New York (US)
  • University of Arizona (US)
Venue
Eukaryotic Cell
Published
2010-03
Volume
9
Issue
3
Pages
405-414
ISSN
  • 1535-9778 (ISSN-L)
  • 1535-9786
OpenAlex
W2120471906
Cited by
63
References
52
Citations by year
2026: 1 · 2025: 4 · 2024: 1 · 2023: 5 · 2021: 3 · 2019: 2 · 2018: 3 · 2017: 5 · 2016: 1 · 2015: 1 · 2014: 9 · 2013: 5 · 2012: 7
FWCI
3.08
Type
journal article
Language
en
Open access
Locations
  • Eukaryotic Cell (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • CUNY Academic Works (City University of New York) (submittedVersion)
Funders
  • National Science Foundation
  • National Institutes of Health (2s07rr005357-30)
  • National Institute of General Medical Sciences (S06 GM 070758, GM 55230, GM 083756, R01GM055230, SC1GM083756, R29GM055230)
  • National Center for Research Resources (RR 05357)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
Keywords
Candida albicans, tandem repeat domain, glycosylation, protein structure, antiparallel beta-sheet, homophilic binding, cell-cell aggregation, protein-protein interaction surfaces, O-glycosylation, N-glycosylation, structure-function relationship, fungal adhesins
MeSH terms
Amino Acid Sequence, Candida albicans, Circular Dichroism, Disaccharides, Enzyme-Linked Immunosorbent Assay, Fibronectins, Fungal Proteins, Glycosylation, Mannosides, Models, Molecular, Molecular Sequence Data, Peptide Fragments, Polystyrenes, Protein Binding, Protein Denaturation, Serine, Threonine, Cell Adhesion Molecules, Sequence Homology, Amino Acid, Protein Structure, Secondary, Protein Structure, Tertiary, Protein Renaturation, Lectins, Protein Interaction Domains and Motifs, Molecular Dynamics Simulation

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