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Structural Basis for Nucleic Acid Binding to the Prion Protein
Author(s) -
Cordeiro Yraima,
Lima Luis Mauricio,
Marques Adriana,
Oliveira Cristiano,
Tinoco Luzineide,
Sampath Srisailam,
Foguel Debora,
Torriani Iris,
Caughey Byron,
Silva Jerson
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a95-a
Subject(s) - nucleic acid , chemistry , dna , transmissible spongiform encephalopathy , prion protein , small molecule , biochemistry , biophysics , plasma protein binding , protein structure , microbiology and biotechnology , computational biology , biology , medicine , disease , pathology , scrapie
The infectious agent of transmissible spongiform encephalopathies (TSE) is believed to comprise, at least in part, the prion protein (PrP). Other molecules can modulate the conversion of the normal PrP C into the pathological conformer (PrP Sc ) but the identity and mechanisms of action of the key physiological factors remain unclear. PrP can specifically recognize nucleic acids with high affinity, resulting in a proteinase K‐resistant and beta‐sheet‐rich protein. Here, we report small‐angle X‐ray scattering, nuclear magnetic resonance spectroscopy and binding assay measurements of the soluble 18‐base pair DNA:PrP 1:1 complex. We demonstrate that, although interaction is mediated mainly through the PrP globular domain, the unstructured region is also recruited to the complex. This visualization of the complex provides insight into how nucleic acid binds to PrP and how it chaperones conformational conversion. Support: CNPq, FAPERJ, CAPES, PRONEX, PADCT.