Universität zu Köln

Daskalov, Asen, Habenstein, Birgit ORCID: 0000-0003-3723-9552, Sabate, Raimon, Berbon, Melanie, Martinez, Denis, Chaignepain, Stephane, Coulary-Salin, Benedicte, Hofmann, Kay ORCID: 0000-0002-2289-9083, Loquet, Antoine ORCID: 0000-0001-7176-7813 and Saupe, Sven J. (2016). Identification of a novel cell death-inducing domain reveals that fungal amyloid-controlled programmed cell death is related to necroptosis. Proc. Natl. Acad. Sci. U. S. A., 113 (10). S. 2720 - 2726. WASHINGTON: NATL ACAD SCIENCES. ISSN 0027-8424

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Abstract

Recent findings have revealed the role of prion-like mechanisms in the control of host defense and programmed cell death cascades. In fungi, HET-S, a cell death-inducing protein containing a HeLo pore-forming domain, is activated through amyloid templating by a Nod-like receptor (NLR). Here we characterize the HELLP protein behaving analogously to HET-S and bearing a new type of N-terminal cell death-inducing domain termed HeLo-like (HELL) and a C-terminal regulatory amyloid motif known as PP. The gene encoding HELLP is part of a three-gene cluster also encoding a lipase (SBP) and a Nod-like receptor, both of which display the PP motif. The PP motif is similar to the RHIM amyloid motif directing formation of the RIP1/RIP3 necrosome in humans. The C-terminal region of HELLP, HELLP(215-278), encompassing the motif, allows prion propagation and assembles into amyloid fibrils, as demonstrated by X-ray diffraction and FTIR analyses. Solid-state NMR studies reveal a well-ordered local structure of the amyloid core residues and a primary sequence that is almost entirely arranged in a rigid conformation, and confirm a beta-sheet structure in an assigned stretch of three amino acids. HELLP is activated by amyloid templating and displays membrane-targeting and cell death-inducing activity. HELLP targets the SBP lipase to the membrane, suggesting a synergy between HELLP and SBP in membrane dismantling. Remarkably, the HeLo-like domain of HELLP is homologous to the pore-forming domain of MLKL, the cell death-execution protein in necroptosis, revealing a transkingdom evolutionary relationship between amyloid-controlled fungal programmed cell death and mammalian necroptosis.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Daskalov, Asen UNSPECIFIED UNSPECIFIED UNSPECIFIED Habenstein, Birgit UNSPECIFIED orcid.org/0000-0003-3723-9552 UNSPECIFIED Sabate, Raimon UNSPECIFIED UNSPECIFIED UNSPECIFIED Berbon, Melanie UNSPECIFIED UNSPECIFIED UNSPECIFIED Martinez, Denis UNSPECIFIED UNSPECIFIED UNSPECIFIED Chaignepain, Stephane UNSPECIFIED UNSPECIFIED UNSPECIFIED Coulary-Salin, Benedicte UNSPECIFIED UNSPECIFIED UNSPECIFIED Hofmann, Kay UNSPECIFIED orcid.org/0000-0002-2289-9083 UNSPECIFIED Loquet, Antoine UNSPECIFIED orcid.org/0000-0001-7176-7813 UNSPECIFIED Saupe, Sven J. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-281633
DOI:	10.1073/pnas.1522361113
Journal or Publication Title:	Proc. Natl. Acad. Sci. U. S. A.
Volume:	113
Number:	10
Page Range:	S. 2720 - 2726
Date:	2016
Publisher:	NATL ACAD SCIENCES
Place of Publication:	WASHINGTON
ISSN:	0027-8424
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PRION-FORMING DOMAIN; MIXED LINEAGE KINASE; HET-S; SIGNAL-TRANSDUCTION; PROTEIN; MECHANISM; MOTIF; INCOMPATIBILITY; PODOSPORA; NECROSIS Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/28163