The Human Disease-Associated Aβ Amyloid Core Sequence Forms Functional Amyloids in a Fungal Adhesin

ABSTRACT There is increasing evidence that many amyloids in living cells have physiological functions. On the surfaces of fungal cells, amyloid core sequences in adhesins can aggregate into 100- to 1,000-nm-wide patches to form high-avidity adhesion nanodomains on the cell surface. The nanodomains f...

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Autores principales:	Rachele D. Rameau, Desmond N. Jackson, Audrey Beaussart, Yves F. Dufrêne, Peter N. Lipke
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2016
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/358f61866c054fd7b5f3a8d69a8297ca
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spelling	oai:doaj.org-article:358f61866c054fd7b5f3a8d69a8297ca2021-11-15T15:49:40ZThe Human Disease-Associated Aβ Amyloid Core Sequence Forms Functional Amyloids in a Fungal Adhesin10.1128/mBio.01815-152150-7511https://doaj.org/article/358f61866c054fd7b5f3a8d69a8297ca2016-03-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01815-15https://doaj.org/toc/2150-7511ABSTRACT There is increasing evidence that many amyloids in living cells have physiological functions. On the surfaces of fungal cells, amyloid core sequences in adhesins can aggregate into 100- to 1,000-nm-wide patches to form high-avidity adhesion nanodomains on the cell surface. The nanodomains form through interactions that have amyloid-like properties: binding of amyloid dyes, perturbation by antiamyloid agents, and interaction with homologous sequences. To test whether these functional interactions are mediated by typical amyloid interactions, we substituted an amyloid core sequence, LVFFA, from human Aβ protein for the native sequence IVIVA in the 1,419-residue Candida albicans adhesin Als5p. The chimeric protein formed cell surface nanodomains and mediated cellular aggregation. The native sequence and chimeric adhesins responded similarly to the amyloid dye thioflavin T and to amyloid perturbants. However, unlike the native protein, the nanodomains formed by the chimeric protein were not force activated and formed less-robust aggregates under flow. These results showed the similarity of amyloid interactions in the amyloid core sequences of native Als5p and Aβ, but they also highlighted emergent properties of the native sequence. Also, a peptide composed of the Aβ amyloid sequence flanked by amino acids from the adhesin formed two-dimensional sheets with sizes similar to the cell surface patches of the adhesins. These results inform an initial model for the structure of fungal cell surface amyloid nanodomains. IMPORTANCE Protein amyloid aggregates are markers of neurodegenerative diseases such as Alzheimer’s and Parkinsonism. Nevertheless, there are also functional amyloids, including biofilm-associated amyloids in bacteria and fungi. In fungi, glycoprotein adhesins aggregate into cell surface patches through amyloid-like interactions, and the adhesin clustering strengthens cell-cell binding. These fungal surface amyloid nanodomains mediate biofilm persistence under flow, and they also moderate host inflammatory responses in fungal infections. To determine whether the amyloid-like properties of fungal surface nanodomains are sequence specific, we ask whether a disease-associated amyloid core sequence has properties equivalent to those of the native sequence in a fungal adhesin. A chimeric adhesin with an amyloid sequence from the Alzheimer’s disease protein Aβ instead of its native sequence effectively clustered the adhesins on the cell surface, but it showed a different response to hydrodynamic shear. These results begin an analysis of the sequence dependence for newly discovered activities for fungal surface amyloid nanodomains.Rachele D. RameauDesmond N. JacksonAudrey BeaussartYves F. DufrênePeter N. LipkeAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 7, Iss 1 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Rachele D. Rameau Desmond N. Jackson Audrey Beaussart Yves F. Dufrêne Peter N. Lipke The Human Disease-Associated Aβ Amyloid Core Sequence Forms Functional Amyloids in a Fungal Adhesin
description	ABSTRACT There is increasing evidence that many amyloids in living cells have physiological functions. On the surfaces of fungal cells, amyloid core sequences in adhesins can aggregate into 100- to 1,000-nm-wide patches to form high-avidity adhesion nanodomains on the cell surface. The nanodomains form through interactions that have amyloid-like properties: binding of amyloid dyes, perturbation by antiamyloid agents, and interaction with homologous sequences. To test whether these functional interactions are mediated by typical amyloid interactions, we substituted an amyloid core sequence, LVFFA, from human Aβ protein for the native sequence IVIVA in the 1,419-residue Candida albicans adhesin Als5p. The chimeric protein formed cell surface nanodomains and mediated cellular aggregation. The native sequence and chimeric adhesins responded similarly to the amyloid dye thioflavin T and to amyloid perturbants. However, unlike the native protein, the nanodomains formed by the chimeric protein were not force activated and formed less-robust aggregates under flow. These results showed the similarity of amyloid interactions in the amyloid core sequences of native Als5p and Aβ, but they also highlighted emergent properties of the native sequence. Also, a peptide composed of the Aβ amyloid sequence flanked by amino acids from the adhesin formed two-dimensional sheets with sizes similar to the cell surface patches of the adhesins. These results inform an initial model for the structure of fungal cell surface amyloid nanodomains. IMPORTANCE Protein amyloid aggregates are markers of neurodegenerative diseases such as Alzheimer’s and Parkinsonism. Nevertheless, there are also functional amyloids, including biofilm-associated amyloids in bacteria and fungi. In fungi, glycoprotein adhesins aggregate into cell surface patches through amyloid-like interactions, and the adhesin clustering strengthens cell-cell binding. These fungal surface amyloid nanodomains mediate biofilm persistence under flow, and they also moderate host inflammatory responses in fungal infections. To determine whether the amyloid-like properties of fungal surface nanodomains are sequence specific, we ask whether a disease-associated amyloid core sequence has properties equivalent to those of the native sequence in a fungal adhesin. A chimeric adhesin with an amyloid sequence from the Alzheimer’s disease protein Aβ instead of its native sequence effectively clustered the adhesins on the cell surface, but it showed a different response to hydrodynamic shear. These results begin an analysis of the sequence dependence for newly discovered activities for fungal surface amyloid nanodomains.
format	article
author	Rachele D. Rameau Desmond N. Jackson Audrey Beaussart Yves F. Dufrêne Peter N. Lipke
author_facet	Rachele D. Rameau Desmond N. Jackson Audrey Beaussart Yves F. Dufrêne Peter N. Lipke
author_sort	Rachele D. Rameau
title	The Human Disease-Associated Aβ Amyloid Core Sequence Forms Functional Amyloids in a Fungal Adhesin
title_short	The Human Disease-Associated Aβ Amyloid Core Sequence Forms Functional Amyloids in a Fungal Adhesin
title_full	The Human Disease-Associated Aβ Amyloid Core Sequence Forms Functional Amyloids in a Fungal Adhesin
title_fullStr	The Human Disease-Associated Aβ Amyloid Core Sequence Forms Functional Amyloids in a Fungal Adhesin
title_full_unstemmed	The Human Disease-Associated Aβ Amyloid Core Sequence Forms Functional Amyloids in a Fungal Adhesin
title_sort	human disease-associated aβ amyloid core sequence forms functional amyloids in a fungal adhesin
publisher	American Society for Microbiology
publishDate	2016
url	https://doaj.org/article/358f61866c054fd7b5f3a8d69a8297ca
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The Human Disease-Associated Aβ Amyloid Core Sequence Forms Functional Amyloids in a Fungal Adhesin

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