XAFS study of the high-affinity copper-binding site of human PrP(91-231) and its low-resolution structure in solution.
Here, we describe the structure of a C-terminal high-affinity copper-binding site within a truncated recombinant human PrP containing residues 91-231, which lacks the octapeptide repeat region. We show that at least two extra co-ordinating groups are involved in binding this copper(II) ion in conjunction with histidine residues 96 and 111 in a region of the molecule known to be critical in conferring strain type. In addition, using X-ray solution scattering, a low-resolution shape of PrP(91-231) is provided. The restored molecular envelope is consistent with the picture where the N-terminal segment, residues 91-120, extends out from the previously known globular domain containing residues 121-231.
Hasnain
S S
SS
CCLRC Daresbury Laboratory, Daresbury, Warrington, Cheshire, UK.
Murphy
L M
LM
Strange
R W
RW
Grossmann
J G
JG
Clarke
A R
AR
Jackson
G S
GS
Collinge
J
J
D001665:Binding Sites; D003300:Copper / Q000378:metabolism*; D006639:Histidine / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D010084:Oxidation-Reduction; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D011328:Prions / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D012542:Scattering, Radiation; D017384:Sequence Deletion / Q000235:genetics; D012996:Solutions; D014965:X-Rays
D010446:Peptide Fragments; D011328:Prions; D011994:Recombinant Proteins; D012996:Solutions; D006639:Histidine; D003300:Copper