A mechanism for copper inhibition of infectious prion conversion
Daniel L Cox 1*, Jianping Pan 1 and Rajiv R Singh 2
1 UC Davis
2 University of California at Davis
* To whom correspondence should be addressed. E-mail: cox{at}physics.ucdavis.edu.
Submitted on February 24, 2006
Revised on March 20, 2006
Accepted on 17 April 2006
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Abstract |
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We employ ab initio electronic structure calculations to obtain two structural models for copper bound in the strongest binding site of the noninfectious form of the prion protein. The models are compatible with available experimental constraints from electron spin resonance data. The bending of the peptide backbone attendant with the copper binding is not compatible with the requisite straight beta-strand backbone structure for the same sequence contained in two recently proposed models of the prion protein structure in its infectious form. We hypothesize that copper binding at this site is protective against conversion to the infectious form, discuss experimental data which appear to support and conflict with our hypothesis, and propose tests using recombinant prion protein, genetically modified cultured neurons, and transgenic mice.
Key Words:
copper, electronic structure theory, prion
