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Table 1 Prion proteins: bona fide prions, prion candidates, and prionoids

From: Protein assembly systems in natural and synthetic biology

Prion

Protein determinant

Function

Prion phenotype

Organism

Prion properties

Reference

Amyloid A

Apolipoprotein, inflammatory response

Amyloid A amyloidosis

Human, cattle, cheetah, chicken, mouse

Amyloid, cell-to-cell spreading, trans-organismal spreading (except for humans)

[43]

[β]

Prb1

Vacuolar proteinase B, protein degradation in vacuole

Phenotypic lag: prolonged carboxypeptidase Y activity after loss of PEP4

Saccharomyces cerevisiae

Non-amyloid, reversibly curable, mitotic inheritance, infectious

[55]

CPEB, Orb2, CPEB3*

Regulating synaptic plasticity, repressor of AMPA receptor transcription

Facilitating long-term memory, activator of AMPA receptor translation

Sea slug, fruit fly, mouse

Self-templating, amyloid, heritable in yeast

[56,57,58]

Cb-Rho prion*

Rho

Transcriptional global regulator

Transcriptional terminator read-through

Clostridium botulinum, Escherichia coli

Amyloid, Sup35C assay, inheritance

[59]

[GAR+]

Pma1/Std1

Proton pump, glucose signaling

Utilization of poor carbon sources in the presence of glucose

Saccharomyces cerevisiae

Inheritance, infectious

[54, 60]

[Het-s]

Het-s

Heterokaryon incompatibility upon mixing with self

Podospora anserina

Dependence on Pa Hsp104, amyloid fibrils infectious

[61, 62]

[LD+]*

Lumini-dependens

Transcription factor controlling autonomous flowering pathway

Hypothetical: delay of flowering

Arabidopsis thaliana

Sup35C assay, detergent resistant aggregates, Hsp70 and Hsp90 dependence, inheritance, infectious

[63, 64]

[LSB+]

Lsb2

Cytoskeletal assembly protein

Seeds [PSI+]

Saccharomyces cerevisiae

Dependence on Hsp104, inheritance, infectious, detergent resistant aggregate

[65]

[MOD+]

Mod5

tRNA isopentenyltransferase

Resistance to azole antifungals, modified sterol biosynthesis

Saccharomyces cerevisiae

Amyloid, Hsp104 dependence, inheritance, infectious

[66, 67]

[MOT3]

Mot3

Transcriptional regulation

Increased biofilm formation, agar invasion, decreased hypoxia resistance

Saccharomyces cerevisiae

Amyloid, dependence on Hsp104, inheritance, infectious

[60, 68]

[NSI+]

Unknown

Unknown

Translational read-through affecting the Sup45 termination factor

Saccharomyces cerevisiae

Sup35C assay, dependence on Hsp104, inheritance, infectious

[60, 69]

[NUP100+]

Nup100

Nuclear pore complex

No significant effect

Saccharomyces cerevisiae

Amyloid, self-assembly, Sup35C assay, dependence on Hsp104, mitotic inheritance

[67, 70, 71]

[OCT+]

Cyc8

Ttranscriptional regulation, chromatin regulation

Derepression of genes inhibited by Cyc8-Tup1 complex, invertase production in the presence of glucose, flocculation

Saccharomyces cerevisiae

Dependence on Hsp104, inheritance, infectious

[60, 72]

[PSI+]

Sup35

Translational termination

Translational read-through

Saccharomyces cerevisiae

Amyloid, Sup35C assay, dependence on Hsp104, inheritance, infectious

[60, 67, 73, 74]

PrP Sc

PRNP

Preserves synaptic structure and function

Fatal neurodegenerative diseases

Human, sheep, cattle, deer, mink, felines

Self-templating, detergent and protease resistant amyloid fibers, infectious

[75]

[RNQ+]

Rnq1

Unknown

Cross-seeding other prions

Saccharomyces cerevisiae

Amyloid, Sup35C assay, dependence on Hsp104, inheritance, infectious

[60, 67, 73, 74]

[SWI+]

Swi1

Transcriptional regulation, nucleosome remodeling

Poor growth on non-glucose carbon sources, abolished multicellular features

Saccharomyces cerevisiae

Amyloid, Sup35C assay, dependence on Hsp104, inheritance, infectious

[60, 67, 73, 74]

[URE3]

Ure2

Gln3 repressor

Utilization of poor nitrogen sources in the presence of ammonium

Saccharomyces cerevisiae

Amyloid, Sup35C assay, inheritance, infectious

[60, 67, 73, 74]

Prionoid

Protein determinant

Function

Prion phenotype

Organism

Prionoid properties

Reference

ASC

Adaptor protein for inflammasome signaling

Inflammasome activation

Human

Non-amyloid helical polymer, cell-to-cell spreading

PYD domain in yeast: Sup35C assay, detergent resistant aggregates, inheritance

[76, 77]

[LEF+]

LEF-10

Viral late expression factor

Downregulation of viral late gene expression

Autographa californica multiple nucleopolyhedrovirus

Sup35C assay, detergent resistant aggregates

[78]

MAVS*

Signal transduction from mitochondrial membrane to cytosol

Activation of MAVS, initiation of antiviral signaling

Human, mouse

Self-templating, detergent and protease-resistant fibers

[79]

[NU+]

New1 PrD

ATP binding cassette protein

Susceptibility to [PSI+] induction

Saccharomyces cerevisiae

Sup35C assay, amyloid,

full New1 protein not shown to form prions

[74, 80] [68]

[NRP+]

Nrp1**

Putative RNA binding protein

 

Saccharomyces cerevisiae

Sup35C assay, detergent-resistant aggregates, Hsp104 dependence

[68, 74]

p53

Transcriptional regulator

Metastasis

Human, mouse

Large cytoplasmic inclusions, cell-to-cell spreading

[43]

Islet amyloid polypeptide (IAPP)

Glycemic regulation

Type 2 diabetes

Human, mouse

Cell-to-cell spreading, self-templating amyloid

[43]

Prion candidates

Organism

Reference

Amyloid A, amyloid-β, −synuclein, β2-microglobulin, immunoglobulin light chain, tau, transthyretin

Human

[43]

ASM4, CBK1, GLN3, GPR1, GTS1, HRP1, KSP1, LSM4, NGR1, NRP1, NSP1, PDR1, PGD1, PUB1, PUF2, RBS1, RLM1, SAP30, YBL081W, YBR016W, YPL184C, YPR022C

Saccharomyces cerevisiae

[68]

ASH1, AZF1, BUD2, CSR2, ERG11, FRE1, GMC1, HAA1, HAP4, HEH2, HRD3, ILV1, JNM1, KAP120, KAP95, MGA1, MPH1, MRN1, MRPL10, MRS3, PBP2, PCL9, PIB1, POL32, PSP1, PUS4, RBS1, RLM1, SAP1, SBE2, SCD5, SED5, SEN15, SLI15, SMP1, SNT1, SPC110, STE20, STE5, UBX7, ULP1, VTS1, YCK3, YGL036W, YFH1, YLR152C

Saccharomyces cerevisiae

[81]

  1. *Validation in non-native host organism. **Incomplete validation. In the prion nomenclature, brackets denote non-Mendelian inheritance and capital letters denote dominance in crosses. Prion properties include: amyloid—prion was shown to form amyloid or detergent resistant aggregates; inheritance—prion is inherited mitotically, meiotically, or as a fusion protein (Sup35C assay); chaperone dependence—prion is dependent on particular chaperones for propagation. Prion candidates are proteins that cannot officially be classified as bona fide prions because they lack experimental validation, but have the potential for inter-organismal spreading