PrionDB: Extraction of mutation data from the literature

2005, PrionDB.

This data was extracted from Medline abstracts and full texts (when available) in an automated manner.

The table below describes the selected point mutation and provides links to other documents. The sentence(s) where the point mutation Q217R was found are listed after the table.

The mutated residues are also indicated in the family sequence alignments and hyperlinked to the corresponding mutation pages.

Point mutation Q217R in PRIO_HUMAN

Point mutation:	Q217R
Domain:	Not determined
General numbering (PrionDB):	-
Protein:	PRIO_HUMAN (PRNP)	Swiss-Prot Cross-reference table Family page
Other point mutations / same protein / same position	Point mutations at position 217 in PRIO_HUMAN
Other point mutations / same protein	List of mutations in PRIO_HUMAN
Family alignments	Mammalian prion proteins Prion proteins (PRP, PRNP)
Other point mutations / same position	Position 217 in Mammalian prion proteins family Position 217 in Prion proteins (PRP, PRNP) family
Reference:	The chaperone protein BiP binds to a mutant prion protein and mediates its degradation by the proteasome. Jin T, Gu Y, Zanusso G, Sy M, Kumar A, Cohen M, Gambetti P, Singh N J Biol Chem 2000 Dec 8;275(49):38699-704.	Medline
Other point mutations / same article	List
Text source	HTML full text
Validation status	True positive

Relevant sentences:

Q217R

We have examined the role of molecular chaperones in the folding of normal and mutant PrP Q217R (PrP217) in transfected neuroblastoma cells
We have now studied the folding and turnover of PrP32 to understand the mechanism by which abnormal PrP forms cause cellular toxicity in our cell culture model and in the human brain carrying the Gerstmann-Sträussler-Scheinker disease Q217R mutation
The mutation at PRNP codon 217 resulting in the substitution of glutamine to arginine (Q217R) in the mutant PrP (PrP217) is associated with a GSS disease phenotype that presents in the seventh decade and is characterized by a slowly progressive dementia associated with cerebellar and extrapyramidal signs (10 )
The histopathological hallmark of the Q217R GSS variant is the presence of PrP217-containing amyloid deposits and neurofibrillary degeneration in the brain tissue (10 )
In a previous study carried out on a transfected neuroblastoma cell model of GSS Q217R , we showed that a significant proportion of PrP217 , which we identified as PrP32 , retains the anchor C-terminal signal peptide , fails to acquire the glycosyl phosphatidylinositol (GPI) anchor , and is retained in the ER by the cellular quality control system
Transfected M17 cells expressing wild type or mutant prion protein (Q217R) were generated as described (9 )
Combined , these experiments clearly show that the 32-kDa band recovered following immunoprecipitation with antibodies to KDEL contains PrP32 and that PrP32 is associated with BiP in the Q217R transfected neuroblastoma cells
BiP interaction with the PrP carrying the Q217R mutation is more complex
The second variant , PrP32 , which accounts for approximately 11% of the total Q217R mutant PrP , is glycosylated but lacks the GPI anchor and carries the uncleaved GPI anchor signal peptide (9 )
For example , the different BiP binding might be related to intrinsic conformational differences between the two Q217R PrP variants
Regardless of the mechanism , it is remarkable that two major types of Q217R mutant PrP , PrP217 and PrP32 , interact differently with BiP , and after this interaction , are processed through different routes
Thus , each of the two forms of Q217R mutant PrP has the potential to perturb the cellular metabolism , but by distinct mechanisms
In conclusion , the present finding , that the two mutant PrP variants generated by the Q217R PRNP mutation are processed through entirely different metabolic pathways , underscores the complexity and diversity of the pathogenic perturbation that may be caused by a simple point mutation

F.Horn (priondbcmbi.ru.nl), 22-Aug-2005