3HAK

Human prion protein variant V129

Summary for 3HAK

• Entry DOI: 10.2210/pdb3hak/pdb
• Related: 3HAF 3HEQ 3HER 3HES
• Descriptor: Major prion protein (2 entities in total)
• Functional Keywords: prion protein, cell membrane, disease mutation, disulfide bond, glycoprotein, golgi apparatus, gpi-anchor, lipoprotein, membrane, polymorphism, prion, membrane protein
• Biological source: Homo sapiens (human)
• Cellular location: Cell membrane; Lipid-anchor, GPI-anchor . Isoform 2: Cytoplasm : P04156
• Total number of polymer chains: 1
• Total formula weight: 12370.71

Authors

Lee, S.,Antony, L.,Hartmann, R.,Knaus, K.J.,Surewicz, K.,Surewicz, W.K.,Yee, V.C. (deposition date: 2009-05-01, release date: 2010-01-12, Last modification date: 2024-10-16)

Primary citation

Lee, S.,Antony, L.,Hartmann, R.,Knaus, K.J.,Surewicz, K.,Surewicz, W.K.,Yee, V.C.
Conformational diversity in prion protein variants influences intermolecular beta-sheet formation.
Embo J., 29:251-262, 2010

PubMed Abstract: A conformational transition of normal cellular prion protein (PrP(C)) to its pathogenic form (PrP(Sc)) is believed to be a central event in the transmission of the devastating neurological diseases known as spongiform encephalopathies. The common methionine/valine polymorphism at residue 129 in the PrP influences disease susceptibility and phenotype. We report here seven crystal structures of human PrP variants: three of wild-type (WT) PrP containing V129, and four of the familial variants D178N and F198S, containing either M129 or V129. Comparison of these structures with each other and with previously published WT PrP structures containing M129 revealed that only WT PrPs were found to crystallize as domain-swapped dimers or closed monomers; the four mutant PrPs crystallized as non-swapped dimers. Three of the four mutant PrPs aligned to form intermolecular beta-sheets. Several regions of structural variability were identified, and analysis of their conformations provides an explanation for the structural features, which can influence the formation and conformation of intermolecular beta-sheets involving the M/V129 polymorphic residue.

PubMed: 19927125
DOI: 10.1038/emboj.2009.333

Experimental method

X-RAY DIFFRACTION (1.8 Å)