Science 29 October 2010:
Vol. 330. no. 6004, pp. 680 - 683
DOI: 10.1126/science.1197785
A Size Threshold Limits Prion Transmission and Establishes Phenotypic Diversity
Aaron Derdowski,1,* Suzanne S. Sindi,1,2,*, Courtney L. Klaips,1 Susanne DiSalvo,1 Tricia R. Serio1,
According to the prion hypothesis, atypical phenotypes arise when a prion protein adopts an alternative conformation and persist when that form assembles into self-replicating aggregates. Amyloid formation in vitro provides a model for this protein-misfolding pathway, but the mechanism by which this process interacts with the cellular environment to produce transmissible phenotypes is poorly understood. Using the yeast prion Sup35/[PSI+], we found that protein conformation determined the size distribution of aggregates through its interactions with a molecular chaperone. Shifts in this range created variations in aggregate abundance among cells because of a size threshold for transmission, and this heterogeneity, along with aggregate growth and fragmentation, induced age-dependent fluctuations in phenotype. Thus, prion conformations may specify phenotypes as population averages in a dynamic system.
1 Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, 185 Meeting Street, Post Office Box G-L2, Providence, RI 02912, USA.
2 Center for Computational Molecular Biology, Brown University, 115 Waterman Street, Post Office Box 1910, Providence, RI 02912, USA.
* These authors contributed equally to this work. 作者: cao1976 时间: 2015-7-27 12:05
atfsu15 发表于 2010-11-2 00:03 ：
不太好说，因为这对解释哺乳动物中的滴度和不同种属的毒株形成机制帮助不大，也解释不了种属屏障。对感染性的解释可能还是得回归到自由能或者能级跃迁上去。作者: cao1976 时间: 2015-7-27 12:06
xuyin 发表于 2010-11-2 13:05：Nature 437, 257-261 (8 September 2005) | doi: 10.1038/nature03989
The most infectious prion protein particles. 作者: cao1976 时间: 2015-7-27 12:09
atfsu15 发表于 2010-11-3 04:10
xuyin发表于 2010-11-2 13:05
xuyin 发表于 2010-11-2 13:05：Nature 437, 257-261 (8 September 2005) | doi: 10.1038/nature03989
The ...