Chen, Pei-Yeh and Lin, Chun-Cheng and Chang, Yin-Ting and Lin, Su-Ching and Chan, Sunney I. (2002) One O-linked sugar can affect the coil-to-β structural transition of the prion peptide. Proceedings of the National Academy of Sciences of the United States of America, 99 (20). pp. 12633-12638. ISSN 0027-8424 http://resolver.caltech.edu/CaltechAUTHORS:CHEpnas02
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It has been known that the structural transition from PrPC to PrPSc leads to the prion formation. This putative conformational change challenges the central dogma of the protein folding theory-"one sequence, one structure." Generally, scientists believe that there must be either a posttranslational modification or environmental factors involved in this event. However, all of the efforts to solve the mystery of the PrPC to PrPSc transition have ended in vain so far. Here we provide evidence linking O-linked glycosylation to the structural transition based on prion peptide studies. We find that the O-linked alpha-GaINAc at Ser-135 suppresses the formation of amyloid fibril formation of the prion peptide at physiological salt concentrations, whereas the peptide with the same sugar at Ser-132 shows the opposite effect. Moreover, this effect is sugar specific. Replacing alpha-GaINAc with beta-GIcNAc does not yield the same effect.
|Additional Information:||Copyright © 2002 by the National Academy of Sciences. Edited by Douglas C. Rees, California Institute of Technology, Pasadena, CA, and approved July 29, 2002 (received for review March 8, 2002). Published online before print September 16, 2002, 10.1073/pnas.192137799. The electron microscopy was obtained on a ZEISS 902 electron microscope in the Institute of Molecular Biology, Academia Sinica, and we thank Dr. Sue Lin-Chao and Ms. Sue-Ping Lee for access to this facility as well as their kind assistance in the use of microscope. This work was supported by a Program Project grant awarded by Academia Sinica as well as a grant from the National Scientific Council, Taiwan (NSC90-2119-M001-010). This paper was submitted directly (Track II) to the PNAS office.|
|Subject Keywords:||TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES; SOLID-PHASE SYNTHESIS; N-ACETYLGLUCOSAMINE; SCRAPIE ISOFORM; ALPHA-HELICES; CELLULAR PRP; PROTEIN; GLYCOSYLATION; PROPAGATION; NUCLEAR|
|Usage Policy:||No commercial reproduction, distribution, display or performance rights in this work are provided.|
|Deposited By:||Tony Diaz|
|Deposited On:||21 Jan 2006|
|Last Modified:||26 Dec 2012 08:44|
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