Dated: Jun 26, 2023

Publication Name: Genetics

Citations : Species-specific protein–protein interactions govern the humanization of the 20S proteasome in yeast

Yeast and humans share thousands of genes despite a billion years of evolutionary divergence. While many human genes can functionally replace their yeast counterparts, nearly half of the tested shared genes cannot. For example, most yeast proteasome subunits are “humanizable,” except subunits comprising the β-ring core, including β2c (HsPSMB7, a constitutive proteasome subunit). We developed a high-throughput pipeline to humanize yeast proteasomes by generating a large library of Hsβ2c mutants and screening them for complementation of a yeast β2 (ScPup1) knockout. Variants capable of replacing ScPup1 included (1) those impacting local protein–protein interactions (PPIs), with most affecting interactions between the β2c C-terminal tail and the adjacent β3 subunit, and (2) those affecting β2c proteolytic activity.
Contributors: Sarmin Sultana, Mudabir Abdullah, Jianhui Li, Mark Hochstrasser, Aashiq H Kachroo

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