NMR structure of the bovine prion protein isolated from healthy calf brains

Hornemann, Simone; Schorn, Christian; Wüthrich, Kurt

doi:10.1038/sj.embor.7400297

Cited by 130 publications

(127 citation statements)

References 30 publications

Supporting

Mentioning

118

Contrasting

Unclassified

Order By: Relevance

“…90-230) with or without typical complex glycoforms indicated that glycosylation did not perturb the structure, and may even stabilize it somewhat. Although these simulations were too short to capture potential large conformational changes, NMR studies on bovine PrP purified from brain extracts indicated that the structure of glycosylated PrP (including the sugar portion of the GPI-anchor) is very similar to recPrP [161]. Recently, longer extensive MD simulations of diglycosylated PrP were reported [53]: DeMarco and Daggett performed 15 ns simulations of human PrP (res.…”

Section: In Vivo Modificationsmentioning

confidence: 99%

Molecular Dynamics as an Approach to Study Prion Protein Misfolding and the Effect of Pathogenic Mutations

Kamp

Daggett

2011

Topics in Current Chemistry

View full text Add to dashboard Cite

Section: In Vivo Modificationsmentioning

confidence: 99%

Molecular Dynamics as an Approach to Study Prion Protein Misfolding and the Effect of Pathogenic Mutations

Kamp

Daggett

2011

Topics in Current Chemistry

View full text Add to dashboard Cite

“…The PrP C structure has been solved by nuclear magnetic resonance (NMR) analysis from recombinant prion protein from a library of vertebrate species [13,21,31,[45][46][47]63]. The global architecture of the various mammalian PrP structures are nearly identical.…”

Section: Prp C Structurementioning

confidence: 99%

A prion disease of cervids: Chronic wasting disease

2008

View full text Add to dashboard Cite

-Chronic wasting disease (CWD) is a prion disease of deer, elk, and moose, initially recognized in Colorado mule deer. The discovery of CWD beyond the borders of Colorado and Wyoming, in Canada and as far east as New York, has led to its emergence as a prion disease of international importance. Epidemiological studies indicate that CWD is horizontally transmitted among free-ranging animals, potentially indirectly by prion-containing secreta or excreta contaminating the environment. Experimental CWD transmission attempts to other wild and domestic mammals and to transgenic mice expressing the prion protein of cattle, sheep, and humans have shed light on CWD species barriers. Transgenic mice expressing the cervid prion protein have proven useful for assessing the genetic influences of Prnp polymorphisms on CWD susceptibility. Accumulating evidence of CWD pathogenesis indicates that the misfolded prion protein or prion infectivity seems to be widely disseminated in many nonneural organs and in blood. This review highlights contemporary research findings in this prion disease of free-ranging wildlife.

show abstract

“…So far, atomic resolution structure determination was focused on recombinant mammalian prion proteins (10)(11)(12)(13)(14)(15)(16)(17)(18), which have recently been shown to represent the protein architecture of PrP C (19). As a group, the mammalian PrPs have Ϸ90% sequence identity (4).…”

mentioning

confidence: 99%

Prion protein NMR structures of chickens, turtles, and frogs

Calzolai

Lysek²,

Pérez³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

168

158

View full text Add to dashboard Cite

The NMR structures of the recombinant prion proteins from chicken (Gallus gallus; chPrP), the red-eared slider turtle (Trachemys scripta; tPrP), and the African clawed frog (Xenopus laevis; xlPrP) are presented. The amino acid sequences of these prion proteins show Ϸ30% identity with mammalian prion proteins. All three species form the same molecular architecture as mammalian PrP C , with a long, flexibly disordered tail attached to the N-terminal end of a globular domain. The globular domain in chPrP and tPrP contains three ␣-helices, one short 310-helix, and a short antiparallel ␤-sheet. In xlPrP, the globular domain includes three ␣-helices and a somewhat longer ␤-sheet than in the other species. The spatial arrangement of these regular secondary structures coincides closely with that of the globular domain in mammalian prion proteins. Based on the low sequence identity to mammalian PrPs, comparison of chPrP, tPrP, and xlPrP with mammalian PrP C structures is used to identify a set of essential amino acid positions for the preservation of the same PrP C fold in birds, reptiles, amphibians, and mammals. There are additional conserved residues without apparent structural roles, which are of interest for the ongoing search for physiological functions of PrP C in healthy organisms.nonmammalian species ͉ transmissible spongiform encephalopathy T he prion protein (PrP) has attracted a lot of interest because of its relation to transmissible spongiform encephalopathies (TSEs), which are a group of invariably fatal neurological diseases (1). Healthy organisms that do not express a prion protein, such as suitably selected transgenic laboratory animals, cannot develop a TSE (2), and the ''protein-only hypothesis'' further attributes TSE-causing infectivity to an aggregated ''scrapie form'' of PrP (PrP SC ) that has been isolated from brain tissue of diseased organisms (1). Although TSEs have only been documented for mammalian species, PrP has been identified in a wider range of higher organisms, which on an evolutionary scale extends at least down to amphibians (3-9). In apparent contrast to the high sequence conservation among mammalian PrPs, no physiological function has been reliably attributed to the ''cellular form'' of PrP (PrP C ) found in healthy organisms.In view of its critical role in TSEs, the prion protein has also attracted considerable interest by structural biologists. So far, atomic resolution structure determination was focused on recombinant mammalian prion proteins (10-18), which have recently been shown to represent the protein architecture of PrP C (19). As a group, the mammalian PrPs have Ϸ90% sequence identity (4). Here, we present the NMR structures of recombinant PrP from chicken, turtle, and frog (chPrP, tPrP, and xlPrP, respectively), each of which has Ϸ30% sequence identity with mammalian PrP. We then exploit this low homology in searches, based on comparison of the three-dimensional structures, for conserved amino acids with apparent roles in maintaining a common PrP C -fold, and for nonst...

show abstract

NMR structure of the bovine prion protein isolated from healthy calf brains

Cited by 130 publications

References 30 publications

Molecular Dynamics as an Approach to Study Prion Protein Misfolding and the Effect of Pathogenic Mutations

Molecular Dynamics as an Approach to Study Prion Protein Misfolding and the Effect of Pathogenic Mutations

A prion disease of cervids: Chronic wasting disease

Prion protein NMR structures of chickens, turtles, and frogs

Contact Info

Product

Resources

About