2jom

From Proteopedia

NMR structure of rabbit prion protein mutation I214V

PDB ID 2jom

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Structural highlights

2jom is a 1 chain structure with sequence from Oryctolagus cuniculus. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

PRIO_RABIT Note=Found in high quantity in the brain of humans and animals infected with degenerative neurological diseases such as kuru, Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler syndrome (GSS), scrapie, bovine spongiform encephalopathy (BSE), transmissible mink encephalopathy (TME), etc.

Function

PRIO_RABIT May play a role in neuronal development and synaptic plasticity. May be required for neuronal myelin sheath maintenance. May play a role in iron uptake and iron homeostasis. Soluble oligomers are toxic to cultured neuroblastoma cells and induce apoptosis (in vitro). Association with GPC1 (via its heparan sulfate chains) targets PRNP to lipid rafts. Also provides Cu(2+) or ZN(2+) for the ascorbate-mediated GPC1 deaminase degradation of its heparan sulfate side chains (By similarity).

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

BACKGROUND: The conformational conversion of the host-derived cellular prion protein (PrP(C)) into the disease-associated scrapie isoform (PrP(Sc)) is responsible for the pathogenesis of transmissible spongiform encephalopathies (TSEs). Various single-point mutations in PrP(C)s could cause structural changes and thereby distinctly influence the conformational conversion. Elucidation of the differences between the wild-type rabbit PrP(C) (RaPrP(C)) and various mutants would be of great help to understand the ability of RaPrP(C) to be resistant to TSE agents. METHODOLOGY/PRINCIPAL FINDINGS: We determined the solution structure of the I214V mutant of RaPrP(C)(91-228) and detected the backbone dynamics of its structured C-terminal domain (121-228). The I214V mutant displays a visible shift of surface charge distribution that may have a potential effect on the binding specificity and affinity with other chaperones. The number of hydrogen bonds declines dramatically. Urea-induced transition experiments reveal an obvious decrease in the conformational stability. Furthermore, the NMR dynamics analysis discloses a significant increase in the backbone flexibility on the pico- to nanosecond time scale, indicative of lower energy barrier for structural rearrangement. CONCLUSIONS/SIGNIFICANCE: Our results suggest that both the surface charge distribution and the intrinsic backbone flexibility greatly contribute to species barriers for the transmission of TSEs, and thereby provide valuable hints for understanding the inability of the conformational conversion for RaPrP(C).

Solution structure and dynamics of the I214V mutant of the rabbit prion protein.,Wen Y, Li J, Xiong M, Peng Y, Yao W, Hong J, Lin D PLoS One. 2010 Oct 7;5(10):e13273. PMID:20949107^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Wen Y, Li J, Xiong M, Peng Y, Yao W, Hong J, Lin D. Solution structure and dynamics of the I214V mutant of the rabbit prion protein. PLoS One. 2010 Oct 7;5(10):e13273. PMID:20949107 doi:10.1371/journal.pone.0013273