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 E200K 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 E200K in PRIO_HUMAN

Point mutation:	E200K
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 200 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 200 in Mammalian prion proteins family Position 200 in Prion proteins (PRP, PRNP) family
Reference:	Identification of a common sphingolipid-binding domain in Alzheimer, prion, and HIV-1 proteins. Mahfoud R, Garmy N, Maresca M, Yahi N, Puigserver A, Fantini J J Biol Chem 2002 Mar 29;277(13):11292-6.	Medline
Other point mutations / same article	List
Text source	HTML full text
Validation status	True positive

Relevant sentences:

E200K

The V3-like domain of PrP is a disulfide-linked loop (Cys179-Cys214) that includes the E200K mutation site associated with familial Creutzfeldt-Jakob disease
The synthetic peptides P1 (KQHTVTTTTKGENFTETDVKMMER) and P2 (KQHTVTTTTKGENFTKTDVKMMER) respectively derived from the human PrP protein and the E200K mutant were purchased from Euro Sequence Gene service (Evry , France)
Increases in the surface pressure induced by the indicated concentrations of peptide P1 (wild-type sequence , squares) or P2 (E200K mutant sequence , circles) added in the aqueous subphase were determined
Effect of Mutation E200K in Human PrP for Sphingolipid Recognition-- The V3-like region of human PrP contains a mutation site (E200K) corresponding to the most common familial form of the Creutzfeldt-Jakob disease (1 )
Another synthetic peptide similar to P1 but bearing the E200K substitution was therefore synthesized (P2) , and its interaction with sphingolipids was also analyzed using the lipid monolayer assay
From a structural point of view , these data are consistent with the high level of structural homology between the wild-type and the E200K mutant of human PrP (27 )
The main effects of the E200K mutation are (i) major changes in the distribution of charges on the protein surface and (ii) the loss of a salt-bridge interaction between the side chains of Glu200 and Lys204
In any case , the E200K mutation has little (if any) effect on the orientation and accessibility of aromatic residues that are involved in binding to GalCer
However , the redistribution of surface charges induced by the E200K mutation may dramatically affect the interaction of PrP with charged lipids such as sphingomyelin
These data show that the E200K mutation specifically affected the recognition of sphingomyelin

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