The DOI matches its Crossref record; 56 of the 59 references it cites were found in a registry or an index.
Functional and Structural Diversity in the Als Protein Family of Candida albicans
Open accessAbstract
The human fungal pathogen Candida albicans colonizes and invades a wide range of host tissues. Adherence to host constituents plays an important role in this process. Two members of the C. albicans Als protein family (Als1p and Als5p) have been found to mediate adherence; however, the functions of other members of this family are unknown. In this study, members of the ALS gene family were cloned and expressed in Saccharomyces cerevisiae to characterize their individual functions. Distinct Als proteins conferred distinct adherence profiles to diverse host substrates. Using chimeric Als5p-Als6p constructs, the regions mediating substrate-specific adherence were localized to the N-terminal domains in Als proteins. Interestingly, a subset of Als proteins also mediated endothelial cell invasion, a previously unknown function of this family. Consistent with these results, homology modeling revealed that Als members contain anti-parallel beta-sheet motifs interposed by extended regions, homologous to adhesins or invasins of the immunoglobulin superfamily. This finding was confirmed using circular dichroism and Fourier transform infrared spectrometric analysis of the N-terminal domain of Als1p. Specific regions of amino acid hypervariability were found among the N-terminal domains of Als proteins, and energy-based models predicted similarities and differences in the N-terminal domains that probably govern the diverse function of Als family members. Collectively, these results indicate that the structural and functional diversity within the Als family provides C. albicans with an array of cell wall proteins capable of recognizing and interacting with a wide range of host constituents during infection.
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In the citing paper
“This gene family encodes eight GPI-linked cell surface proteins that mediate binding to diverse host substrates [20][21][22][23][24][25].”
From Als3 Is a Candida albicans Invasin That Binds to Cadherins and Induces Endocytosis by Host Cells (2007) · cites this paper as [23]
In the citing paper
“We found that Saccharomyces cerevisiae expressing Als3 were avidly endocytosed by endothelial cells.”
From Als3 Is a Candida albicans Invasin That Binds to Cadherins and Induces Endocytosis by Host Cells (2007) · cites this paper as [23]
In the citing paper
“Also, we found that S. cerevisiae expressing Als3 bound to both endothelial cells and FaDu oral epithelial cells [23].”
From Als3 Is a Candida albicans Invasin That Binds to Cadherins and Induces Endocytosis by Host Cells (2007) · cites this paper as [23]
In the citing paper
“Similar experiments suggested that Als1 and Als5 could also induce endocytosis, although with considerably less efficiency than Als3 [23].”
From Als3 Is a Candida albicans Invasin That Binds to Cadherins and Induces Endocytosis by Host Cells (2007) · cites this paper as [23]
In the citing paper
“The N-terminal domain contains the substratebinding region [23,26].”
From Als3 Is a Candida albicans Invasin That Binds to Cadherins and Induces Endocytosis by Host Cells (2007) · cites this paper as [23]
In the citing paper
“Computer-assisted modeling of the N-termini of Als1, Als3, and Als5 predicts the presence of antiparallel b sheets that define the immunoglobulin superfamily [23].”
From Als3 Is a Candida albicans Invasin That Binds to Cadherins and Induces Endocytosis by Host Cells (2007) · cites this paper as [23]
In the citing paper
“Previously, we determined that the N-terminal region of Als proteins contains the substrate-binding site [23,26].”
From Als3 Is a Candida albicans Invasin That Binds to Cadherins and Induces Endocytosis by Host Cells (2007) · cites this paper as [23]
In the citing paper
“The Als family of proteins contains six members in addition to Als1 and Als3 [20][21][22][23][24][25].”
From Als3 Is a Candida albicans Invasin That Binds to Cadherins and Induces Endocytosis by Host Cells (2007) · cites this paper as [23]
In the citing paper
“When expressed in S. cerevisiae, Als5 induces weak endothelial cell endocytosis similar to that induced by Als1 [23].”
From Als3 Is a Candida albicans Invasin That Binds to Cadherins and Induces Endocytosis by Host Cells (2007) · cites this paper as [23]
In the citing paper
“Previously, we have reported that S. cerevisiae expressing Als1 or Als3 binds to a variety of host constituents, including endothelial cells, epithelial cells, laminin, and fibronectin [23].”
From Als3 Is a Candida albicans Invasin That Binds to Cadherins and Induces Endocytosis by Host Cells (2007) · cites this paper as [23]
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“cerevisiae promotes binding to several different protein-coated substrate”
Als3 Is a Candida albicans Invasin That Binds to Cadherins and Induces Endocytosis by Host Cells
Phan, Q. T., Myers, C. L., Fu, Y., Sheppard, D. C., Yeaman, M. R., Welch, W. H., Ibrahim, A. S., Edwards, J. E., & Filler, S. G. (2007) · PLoS Biology · doi:10.1371/journal.pbio.0050064 · Cited by 641
“cerevisiae expressing Als3 are endocytosed by endothelial cells [23].”
BackgroundResultInfluentialSelf-citationFlocculation, adhesion and biofilm formation in yeasts
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Critical Role of Bcr1-Dependent Adhesins in C. albicans Biofilm Formation In Vitro and In Vivo
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“This close relationship is reflected by their similar substrate binding properties [29].”
BackgroundMethodSelf-citation
Metadata
- Authors
- Sheppard, D. C., Yeaman, M. R., Welch, W. H., Phan, Q. T., Fu, Y., Ibrahim, A. S., Filler, S. G., Zhang, M., Waring, A. J., & Edwards, J. E.
- Affiliations
- University of California, Los Angeles (US)
- University of Nevada, Reno (US)
- California State University, Long Beach (US)
- Corresponding author
- Sheppard, Donald C.
- ORCID
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2004-07
- Volume
- 279
- Issue
- 29
- Pages
- 30480-30489
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1968095975
- Cited by
- 300
- References
- 59
- Citations by year
- 2026: 9 · 2025: 7 · 2024: 5 · 2023: 9 · 2022: 10 · 2021: 15 · 2020: 15 · 2019: 7 · 2018: 14 · 2017: 11 · 2016: 11 · 2015: 12 · 2014: 27 · 2013: 16 · 2012: 13
- FWCI
- 6.17
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (P01 AI-37194, R01AI019990, R01 AI-48031, R03AI054531, R01-AI19990, R01AI054928, R01AI048031, P01AI037194)
- National Institute of Dental and Craniofacial Research (R01DE013974, 5R01 DE13974)
- National Center for Research Resources (M01RR000425, M01-RR00425)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Health Sciences › Medicine › Infectious Diseases › Fungal Infections and Studies
- Keywords
- Candida albicans, fungal adhesion, endothelial cell invasion, N-terminal domain, antiparallel beta-sheet, cell wall proteins, host-pathogen interaction, fusion protein
- MeSH terms
- Amino Acid Sequence, Candida albicans, Cell Adhesion, Cell Wall, Circular Dichroism, Cloning, Molecular, Endothelium, Vascular, Epithelial Cells, Flow Cytometry, Fungal Proteins, Multigene Family, Humans, Membrane Glycoproteins, Models, Molecular, Molecular Sequence Data, Plasmids, Recombinant Fusion Proteins, Saccharomyces cerevisiae, Substrate Specificity, Cell Adhesion Molecules, Polymerase Chain Reaction, Protein Structure, Secondary, Protein Structure, Tertiary, Spectroscopy, Fourier Transform Infrared, DNA Primers, Amino Acid Motifs, Cell Line, Tumor
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