Entry created on 1 July 2019 (Revision 1.0) Annotator: Tamás Horváth
This entry is part of a multi-component system encompassing the following entries: P04156 P05067
Basic protein information
Accession P05067
Common name Amyloid-beta oligomer
Gene APP
Organism Homo sapiens
Uniprot name Amyloid-beta A4 protein
Basic LLPS information
Organelle cytoplasmic protein granule
Type of experimental evidence
Joined entry P04156 P05067
Protein region(s) mediating LLPS
672
-
713
Amyloid-forming region
Based on the experimental results of the following publication: 30401430
Molecular features viewer
PDB structures
Extended LLPS information
Functional description
PrP^C creates a hydrogel in crowded phisiological conditions with ~12- or ~50-mer Amiloid beta oligomers (Aβo). In the hydrogel PrP^C is moderately to highly mobile, depending on the ratio of Aβo to PrP^C. Aβo seems to be highly coordinated in the gel, and does not show mobility. Major secondary structure changes are observed for hydrogel PrP^C. In monomeric PrP^C, the 40 Gly of the N-term and the six Ala of the linker region (aa 113–120) are unstructured. The vast majority of these residues exhibit a-helical character in the hydrogel. This conformational shift spans PrP^C regions for mGluR5 and Aβo interaction. PrP^C regions 23-51, and 91-111 bind to Aβo (PMID:30401430).
Literature supporting the LLPS: 30401430
Functional class of membraneless organelle: not known/not clear
Binding partners (at biological protein concentrations)
1) PrP^C (strictly required for LLPS) 2) Metabotropic glutamate receptor 5 (mGluR5) (not strictly required)
Type of RNA(s) required/used for the LLPS at biological protein concentrations
Not required.
Molecular interaction types contributing to LLPS
Not known (PMID:30401430)
Determinants of phase separation and droplet properties
1) crowding agent concentration 2) stoichiometry of the components 3) pH 4) salt concentration
Membrane cluster No
Partner-dependent Yes
RNA-dependent No
PTM required No
Domain-motif interactions Not known
Discrete oligomerization No
Regulation and disease
Post-translational modifications affecting LLPS
Position Residue PTM Effect Reference Modifying enzyme Notes
Isoforms known to affect LLPS
Isoform Effect Reference
All known isoforms containing sequence changes in the LLPS region(s)
Position type Isoform names from UniProt
Disease mutations affecting LLPS
Mutation dbSNP Disease OMIM Effect Reference Notes
Experimental information
Experimental techniques applied to prove/investigate LLPS
To further illustrate dynamic exchange of hydrogel PrPC in vitro, Alexa 568-tagged PrPC (fluorescent tagging) was added to hydrogels containing PrP-FAM or Aβo-FAM. Alexa 568 PrPC readily enters FAM-Aβo/PrP hydrogels, resulting in orange signal (co-localization). For PrP-FAM hydrogels, PrP-Alexa 568 incorporation decreases FAM signal, while for Aβo-FAM hydrogels there is no change (co-localization). Thus, FRAP shows high PrPC diffusivity within hydrogels. Both FRAP and ssNMR demonstrate that Aβo is held fixed in hydrogels, unable to either rotate or translate detectably (morphology). In vivo: unidentified cellular constituents or PrP^C glycosylation may stabilize cellular hydrogel (PMID:30401430).
Experimental observations supporting the liquid material state of the condensate
dynamic exchange of molecules with surrounding solvent (PMID:30401430) reversibility of formation and dissolution (PMID:30401430)