Domain organization and structure-function relationship of the HET-s prion protein of Podospora anserina.
The [Het-s] infectious element of the fungus Podospora anserina is a prion protein involved in a genetically controlled cell death reaction termed heterokaryon incompatibility. Previous analyses indicate that [Het-s] propagates as a self-perpetuating amyloid aggregate. The HET-s protein is 289 amino acids in length. Herein, we identify the region of the HET-s protein that is responsible for amyloid formation and prion propagation. The region of HET-s spanning residues 218-289 forms amyloid fibers in vitro and allows prion propagation in vivo. Conversely, a C-terminal deletion in HET-s prevents amyloid aggregation in vitro and prion propagation in vivo, and abolishes the incompatibility function. In the soluble form of HET-s, the region from residue 1 to 227 forms a well-folded domain while the C-terminal region is highly flexible. Together, our data establish a domain structure-function relationship for HET-s amyloid formation, prion propagation and incompatibility activity.
Laboratoire de Génétique Moléculaire des Champignons, Service de Microscopie, UMR 5095 CNRS/Université de Bordeaux 2, 1 rue Camille St Saëns, 33077 Bordeaux cedex, France.
Axelle
A
Balguerie
Suzana
S
Dos Reis
Christiane
C
Ritter
Stéphane
S
Chaignepain
Bénédicte
B
Coulary-Salin
Vincent
V
Forge
Katell
K
Bathany
Ioan
I
Lascu
Jean-Marie
JM
Schmitter
Roland
R
Riek
Sven J
SJ
Saupe
D000595:Amino Acid Sequence; D002942:Circular Dichroism; D005656:Fungal Proteins / Q000737:chemistry* / Q000502:physiology*; D006868:Hydrolysis; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D020037:Sordariales / Q000378:metabolism*; D017550:Spectroscopy, Fourier Transform Infrared; D013329:Structure-Activity Relationship
D005656:Fungal Proteins; C083891:HET-S protein, Podospora anserina; D011994:Recombinant Proteins