An Aggregation-Specific Enzyme-Linked Immunosorbent Assay: Detection of Conformational Differences between Recombinant PrP Protein Dimers and PrP Sc Aggregates

Author:

Pan Tao1,Chang Binggong1,Wong Poki1,Li Chaoyang1,Li Ruliang1,Kang Shin-Chung1,Robinson John D.2,Thompsett Andrew R.3,Tein Po4,Yin Shaoman4,Barnard Geoff5,McConnell Ian5,Brown David R.3,Wisniewski Thomas6,Sy Man-Sun2

Affiliation:

1. Institute of Pathology

2. Department of Neurosciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44107-1712

3. Department of Biology and Biochemistry, Bath University, Bath, United Kingdom

4. Institute of Microbiology, Chinese Academy of Science, Beijing 100080, People's Republic of China

5. Centre for Veterinary Science, Department of Clinical Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom

6. Department of Neurology, Psychiatry and Pathology, New York University School of Medicine, New York, New York 10016

Abstract

ABSTRACT The conversion of the normal cellular prion protein, PrP C , into the protease-resistant, scrapie PrP Sc aggregate is the cause of prion diseases. We developed a novel enzyme-linked immunosorbent assay (ELISA) that is specific for PrP aggregate by screening 30 anti-PrP monoclonal antibodies (MAbs) for their ability to react with recombinant mouse, ovine, bovine, or human PrP dimers. One MAb that reacts with all four recombinant PrP dimers also reacts with PrP Sc aggregates in ME7-, 139A-, or 22L-infected mouse brains. The PrP Sc aggregate is proteinase K resistant, has a mass of 2,000 kDa or more, and is present at a time when no protease-resistant PrP is detectable. This simple and sensitive assay provides the basis for the development of a diagnostic test for prion diseases in other species. Finally, the principle of the aggregate-specific ELISA we have developed may be applicable to other diseases caused by abnormal protein aggregation, such as Alzheimer's disease or Parkinson's disease.

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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