Accessibility of a critical prion protein region involved in strain recognition and its implications for the early detection of prions

Cellular and Molecular Life Sciences : CMLS
Jue YuanW Q Zou

Abstract

Human prion diseases are characterized by the accumulation in the brain of proteinase K (PK)-resistant prion protein designated PrP27 - 30 detectable by the 3F4 antibody against human PrP109 - 112. We recently identified a new PK-resistant PrP species, designated PrP*20, in uninfected human and animal brains. It was preferentially detected with the 1E4 antibody against human PrP 97 - 108 but not with the anti-PrP 3F4 antibody, although the 3F4 epitope is adjacent to the 1E4 epitope in the PrP*20 molecule. The present study reveals that removal of the N-terminal amino acids up to residue 91 significantly increases accessibility of the 1E4 antibody to PrP of brains and cultured cells. In contrast to cells expressing wild-type PrP, cells expressing pathogenic mutant PrP accumulate not only PrP*20 but also a small amount of 3F4-detected PK-resistant PrP27 - 30. Remarkably, during the course of human prion disease, a transition from an increase in 1E4-detected PrP*20 to the occurrence of the 3F4-detected PrP27 - 30 was observed. Our study suggests that an increase in the level of PrP*20 characterizes the early stages of prion diseases.

Citations

Nov 9, 2010·Acta Neuropathologica·Pierluigi GambettiWitold K Surewicz
May 18, 2011·Journal of Molecular Neuroscience : MN·Pierluigi GambettiWen-Quan Zou
Mar 3, 2010·The Journal of Biological Chemistry·Wen-Quan ZouJian-Ping Guo
Oct 17, 2012·Journal of Visualized Experiments : JoVE·Xiangzhu XiaoWen-Quan Zou
Nov 25, 2014·Emerging Infectious Diseases·Silvio NotariPierluigi Gambetti
Jan 14, 2009·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·M Jake PushieHans J Vogel
Jun 24, 2008·Annals of Neurology·Pierluigi GambettiWen-Quan Zou
Aug 10, 2010·Annals of Neurology·Wen-Quan ZouPierluigi Gambetti
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Mar 12, 2011·The Journal of Biological Chemistry·Wen-Quan ZouJian-Ping Guo
May 23, 2014·Alzheimer Disease and Associated Disorders·Nupur GhoshalNigel J Cairns
May 27, 2016·Clinical Microbiology Reviews·Alvin S Das, Wen-Quan Zou

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