5L6R

PrP226* - Solution-state NMR structure of truncated human prion protein

Summary for 5L6R

• Entry DOI: 10.2210/pdb5l6r/pdb
• NMR Information: BMRB: 34003
• Descriptor: Major prion protein (1 entity in total)
• Functional Keywords: truncated form of human prion protein, binds to mab v5b2, structure from cyana 3.0, transport protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 16595.45

Authors

Kovac, V.,Zupancic, B.,Ilc, G.,Curin Serbec, V.,Plavec, J. (deposition date: 2016-05-31, release date: 2016-10-05, Last modification date: 2024-10-16)

Primary citation

Kovac, V.,Zupancic, B.,Ilc, G.,Plavec, J.,Curin Serbec, V.
Truncated prion protein PrP226* - A structural view on its role in amyloid disease.
Biochem. Biophys. Res. Commun., 484:45-50, 2017

PubMed Abstract: In the brain of patients with transmissible spongiform encephalopathies, besides PrP aggregates, deposition of truncated PrP molecules was described. Jansen et al. reported two clinical cases with deposition of C-terminally truncated PrP, one of them ending with Tyr226. We have previously described the discovery of monoclonal antibody V5B2 that selectively recognizes this version of the prion protein, which we called PrP226*. Using monoclonal antibody V5B2 we showed that accumulation of PrP226* is characteristic for most types of human and animal TSEs. Its distribution correlates to the distribution of PrP aggregates. To gain insight into the structural basis of its presence and distribution in PrP aggregates, we have determined the NMR structure of recombinant PrP226*. The structure of the protein consists of a disordered N-terminal part (residues 90-125) and a structured C-terminal part (residues 126-226). The C-terminal segment consists of four α-helices and a short antiparallel β-sheet. Our model predicts a break in the C-terminal helix and reorganized hydrophobic interactions between helix α and β-α loop due to the shorter C-terminus. The structural model gives information on the possible role of the protein in the development of amyloid disease and can serve as a foundation to develop tools for prevention and treatment of prion diseases.

PubMed: 28109886
DOI: 10.1016/j.bbrc.2017.01.078

Experimental method

SOLUTION NMR