Native-State Stability Determines the Extent of Degradation Relative to Secretion of Protein Variants from Pichia pastoris

@inproceedings{Whyteside2011NativeStateSD,
  title={Native-State Stability Determines the Extent of Degradation Relative to Secretion of Protein Variants from Pichia pastoris},
  author={Graham Whyteside and Marcos Julio Caruso Alcocer and Janet R Kumita and Christopher M. Dobson and Maria Lazarou and Richard J Pleass and David B. Archer},
  booktitle={PloS one},
  year={2011}
}
We have investigated the relationship between the stability and secreted yield of a series of mutational variants of human lysozyme (HuL) in Pichia pastoris. We show that genes directly involved in the unfolded protein response (UPR), ER-associated degradation (ERAD) and ER-phagy are transcriptionally up-regulated more quickly and to higher levels in response to expression of more highly-destabilised HuL variants and those variants are secreted to lower yield. We also show that the less stable… CONTINUE READING
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