Domain Organization and Structure-function Relationship of the HET-s Prion Protein of Podospora Anserina

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2003 May 3

PMID 12727874

Citations 82

Authors

Axelle Balguerie

Suzana Dos Reis

Christiane Ritter

Stephane Chaignepain

Benedicte Coulary-Salin

Vincent Forge

Katell Bathany

Ioan Lascu

Jean-Marie Schmitter

Roland Riek

Sven J Saupe

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

A Story Between s and S: [Het-s] Prion of the Fungus .

Son M Mycobiology. 2024; 52(2):85-91.

PMID: 38690032 PMC: 11057395. DOI: 10.1080/12298093.2024.2322211.

Vaccination with structurally adapted fungal protein fibrils induces immunity to Parkinson's disease.

Pesch V, Flores-Fernandez J, Reithofer S, Ma L, Ozduzenciler P, Busch Y Brain. 2024; 147(5):1644-1652.

PMID: 38428032 PMC: 11068327. DOI: 10.1093/brain/awae061.

Deep orange gene editing triggers temperature-sensitive lethal phenotypes in Ceratitis capitata.

Sollazzo G, Nikolouli K, Gouvi G, Aumann R, Schetelig M, Bourtzis K BMC Biotechnol. 2024; 24(1):7.

PMID: 38302991 PMC: 10835909. DOI: 10.1186/s12896-024-00832-x.

Emergence of the fungal immune system.

Daskalov A iScience. 2023; 26(6):106793.

PMID: 37213230 PMC: 10197012. DOI: 10.1016/j.isci.2023.106793.

Exploring a diverse world of effector domains and amyloid signaling motifs in fungal NLR proteins.

Wojciechowski J, Tekoglu E, Gasior-Glogowska M, Coustou V, Szulc N, Szefczyk M PLoS Comput Biol. 2022; 18(12):e1010787.

PMID: 36542665 PMC: 9815663. DOI: 10.1371/journal.pcbi.1010787.

References

Tuite M . Yeast prions and their prion-forming domain. Cell. 2000; 100(3):289-92. DOI: 10.1016/s0092-8674(00)80663-7. View

Dobson C . Protein misfolding, evolution and disease. Trends Biochem Sci. 1999; 24(9):329-32. DOI: 10.1016/s0968-0004(99)01445-0. View

Saupe S . Molecular genetics of heterokaryon incompatibility in filamentous ascomycetes. Microbiol Mol Biol Rev. 2000; 64(3):489-502. PMC: 99001. DOI: 10.1128/MMBR.64.3.489-502.2000. View

Flechsig E, Shmerling D, Hegyi I, Raeber A, Fischer M, Cozzio A . Prion protein devoid of the octapeptide repeat region restores susceptibility to scrapie in PrP knockout mice. Neuron. 2000; 27(2):399-408. DOI: 10.1016/s0896-6273(00)00046-5. View

Supattapone S, Muramoto T, Legname G, Mehlhorn I, Cohen F, DeArmond S . Identification of two prion protein regions that modify scrapie incubation time. J Virol. 2001; 75(3):1408-13. PMC: 114047. DOI: 10.1128/JVI.75.3.1408-1413.2001. View

Glass N, Jacobson D, Shiu P . The genetics of hyphal fusion and vegetative incompatibility in filamentous ascomycete fungi. Annu Rev Genet. 2000; 34:165-186. DOI: 10.1146/annurev.genet.34.1.165. View

Thual C, Bousset L, Komar A, Walter S, Buchner J, Cullin C . Stability, folding, dimerization, and assembly properties of the yeast prion Ure2p. Biochemistry. 2001; 40(6):1764-73. DOI: 10.1021/bi001916l. View

Wuthrich K, Riek R . Three-dimensional structures of prion proteins. Adv Protein Chem. 2001; 57:55-82. DOI: 10.1016/s0065-3233(01)57018-7. View

Scheibel T, Lindquist S . The role of conformational flexibility in prion propagation and maintenance for Sup35p. Nat Struct Biol. 2001; 8(11):958-62. DOI: 10.1038/nsb1101-958. View

10.

Dos Reis S, Coulary-Salin B, Forge V, Lascu I, Begueret J, Saupe S . The HET-s prion protein of the filamentous fungus Podospora anserina aggregates in vitro into amyloid-like fibrils. J Biol Chem. 2001; 277(8):5703-6. DOI: 10.1074/jbc.M110183200. View

11.

Maddelein M, Begueret J, Saupe S . In vivo aggregation of the HET-s prion protein of the fungus Podospora anserina. Mol Microbiol. 2002; 42(5):1325-35. DOI: 10.1046/j.1365-2958.2001.02707.x. View

12.

Baxa U, Speransky V, Steven A, Wickner R . Mechanism of inactivation on prion conversion of the Saccharomyces cerevisiae Ure2 protein. Proc Natl Acad Sci U S A. 2002; 99(8):5253-60. PMC: 122756. DOI: 10.1073/pnas.082097899. View

13.

Maddelein M, Dos Reis S, Duvezin-Caubet S, Coulary-Salin B, Saupe S . Amyloid aggregates of the HET-s prion protein are infectious. Proc Natl Acad Sci U S A. 2002; 99(11):7402-7. PMC: 124243. DOI: 10.1073/pnas.072199199. View

14.

Bousset L, Thomson N, Radford S, Melki R . The yeast prion Ure2p retains its native alpha-helical conformation upon assembly into protein fibrils in vitro. EMBO J. 2002; 21(12):2903-11. PMC: 126058. DOI: 10.1093/emboj/cdf303. View

15.

Roepstorff P, Fohlman J . Proposal for a common nomenclature for sequence ions in mass spectra of peptides. Biomed Mass Spectrom. 1984; 11(11):601. DOI: 10.1002/bms.1200111109. View

16.

Punt P, Dingemanse M, Pouwels P, van den Hondel C . Isolation and characterization of the glyceraldehyde-3-phosphate dehydrogenase gene of Aspergillus nidulans. Gene. 1988; 69(1):49-57. DOI: 10.1016/0378-1119(88)90377-0. View

17.

Hirel P, Schmitter M, Dessen P, Fayat G, Blanquet S . Extent of N-terminal methionine excision from Escherichia coli proteins is governed by the side-chain length of the penultimate amino acid. Proc Natl Acad Sci U S A. 1989; 86(21):8247-51. PMC: 298257. DOI: 10.1073/pnas.86.21.8247. View

18.

Berges T, Barreau C . Heat shock at an elevated temperature improves transformation efficiency of protoplasts from Podospora anserina. J Gen Microbiol. 1989; 135(3):601-4. DOI: 10.1099/00221287-135-3-601. View

19.

Turcq B, Deleu C, Denayrolles M, Begueret J . Two allelic genes responsible for vegetative incompatibility in the fungus Podospora anserina are not essential for cell viability. Mol Gen Genet. 1991; 228(1-2):265-9. DOI: 10.1007/BF00282475. View

20.

Deleu C, Clave C, Begueret J . A single amino acid difference is sufficient to elicit vegetative incompatibility in the fungus Podospora anserina. Genetics. 1993; 135(1):45-52. PMC: 1205625. DOI: 10.1093/genetics/135.1.45. View