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Cu 2+ binding triggers αBoPrP assembly into insoluble laminar polymers
Author(s) -
González-Iglesias Reinerio,
Elvira Gema,
Rodrı́guez-Navarro José A,
Vélez Marisela,
Calero Miguel,
Pajares Marı́a A,
Gasset Marı́a
Publication year - 2004
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(03)01397-8
Subject(s) - chemistry , prion protein , polymer , nucleation , crystallography , sequence (biology) , biophysics , molecule , ligand (biochemistry) , small molecule , biochemistry , receptor , biology , organic chemistry , medicine , disease , pathology
Cu 2+ binding is so far the best characterized property of the prion protein. This interaction has been mapped to the N‐terminal domain of the prion protein where multiple His residues occur largely embedded within the repetitive PHGGGWGQ sequence known as octarepeats. When Cu 2+ interaction is studied using a solution of full‐length bovine prion protein containing six octarepeats at protein concentrations above 25 μM, a drastic increase in solution turbidity is observed due to the formation of insoluble cation–protein complexes that appear as bidimensional polymer meshes. These bidimensional meshes consist of a single layer of protein molecules crosslinked by Cu 2+ cations. Polymer formation is a cooperative process that proceeds by nucleation of protein molecules with a Cu 2+ site occupancy of above 2. These results support the hypothesis that the N‐terminal domain of prion protein is a ligand binding module that promotes crosslinked assembly, and suggest the existence of inter‐repeat Cu 2+ sites.