Als3 Is a Candida albicans Invasin That Binds to Cadherins and Induces Endocytosis by Host Cells
Quynh T. Phan,Carter L. Myers,Yue Fu,Yue Fu,Donald C. Sheppard,Michael R. Yeaman,Michael R. Yeaman,William Welch,Ashraf S. Ibrahim,Ashraf S. Ibrahim,John E. Edwards,John E. Edwards,Scott G. Filler,Scott G. Filler +13 more
TLDR
Als3 is a fungal invasin that mimics host cell cadherins and induces endocytosis by binding to N-cadherin on endothelial cells and E-cadaverin on oral epithelial cells.Abstract:
Candida albicans is the most common cause of hematogenously disseminated and oropharyngeal candidiasis. Both of these diseases are characterized by fungal invasion of host cells. Previously, we have found that C. albicans hyphae invade endothelial cells and oral epithelial cells in vitro by inducing their own endocytosis. Therefore, we set out to identify the fungal surface protein and host cell receptors that mediate this process. We found that the C. albicans Als3 is required for the organism to be endocytosed by human umbilical vein endothelial cells and two different human oral epithelial lines. Affinity purification experiments with wild-type and an als3Δ/als3Δ mutant strain of C. albicans demonstrated that Als3 was required for C. albicans to bind to multiple host cell surface proteins, including N-cadherin on endothelial cells and E-cadherin on oral epithelial cells. Furthermore, latex beads coated with the recombinant N-terminal portion of Als3 were endocytosed by Chinese hamster ovary cells expressing human N-cadherin or E-cadherin, whereas control beads coated with bovine serum albumin were not. Molecular modeling of the interactions of the N-terminal region of Als3 with the ectodomains of N-cadherin and E-cadherin indicated that the binding parameters of Als3 to either cadherin are similar to those of cadherin–cadherin binding. Therefore, Als3 is a fungal invasin that mimics host cell cadherins and induces endocytosis by binding to N-cadherin on endothelial cells and E-cadherin on oral epithelial cells. These results uncover the first known fungal invasin and provide evidence that C. albicans Als3 is a molecular mimic of human cadherins.read more
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References
More filters
Journal ArticleDOI
The Amber biomolecular simulation programs
David A. Case,Thomas E. Cheatham,Tom Darden,Holger Gohlke,Ray Luo,Kenneth M. Merz,Alexey V. Onufriev,Carlos Simmerling,Bing Wang,Robert J. Woods +9 more
TL;DR: The development, current features, and some directions for future development of the Amber package of computer programs, which contains a group of programs embodying a number of powerful tools of modern computational chemistry, focused on molecular dynamics and free energy calculations of proteins, nucleic acids, and carbohydrates.
Journal ArticleDOI
Culture of Human Endothelial Cells Derived from Umbilical Veins. IDENTIFICATION BY MORPHOLOGIC AND IMMUNOLOGIC CRITERIA
TL;DR: It is demonstrated that it is possible to culture morphologically and immunologically identifiable human endothelial cells for periods up to 5 mo and ABH antigens appropriate to the tissue donor's blood type were not detectable on cultured smooth muscle cells or fibroblasts.
Journal ArticleDOI
SWISS-MODEL: an automated protein homology-modeling server
TL;DR: The SWISS-MODEL server is under constant development to improve the successful implementation of expert knowledge into an easy-to-use server.
Journal ArticleDOI
Nonfilamentous C. albicans mutants are avirulent.
Hsiu-Jung Lo,Julia R. Köhler,Julia R. Köhler,Beth DiDomenico,David Loebenberg,Anthony Cacciapuoti,Gerald R. Fink +6 more
TL;DR: This Candida cph1/cph1 efg1/efg1 double mutant, locked in the yeast form, is avirulent in a mouse model.
Journal ArticleDOI
FUGUE: sequence-structure homology recognition using environment-specific substitution tables and structure-dependent gap penalties.
TL;DR: It is demonstrated that the combination of these three key features implemented in FUGUE improves both homology recognition performance and alignment accuracy.