biostudies-literatureSerohijos AWNIGMS NIH HHSL1-3https://www.ebi.ac.uk/biostudies/studies/S-EPMC3566449biostudies-literatureUnknown104(3)To understand the variation of protein sequences in nature, we need to reckon with evolutionary constraints that are biophysical, cellular, and ecological. Here, we show that under the global selection against protein misfolding, there exists a scaling among protein folding stability, protein cellular abundance, and effective population size. The specific scaling implies that the several-orders-of-magnitude range of protein abundances in the cell should leave imprints on extant protein structures, a prediction that is supported by our structural analysis of the yeast proteome.Biophysical journalHighly abundant proteins favor more stable 3D structures in yeast.PMC3566449R01 GM068670Lee SYSerohijos AWShakhnovich EIfalseHighly abundant proteins favor more stable 3D structures in yeast.To understand the variation of protein sequences in nature, we need to reckon with evolutionary constraints that are biophysical, cellular, and ecological. Here, we show that under the global selection against protein misfolding, there exists a scaling among protein folding stability, protein cellular abundance, and effective population size. The specific scaling implies that the several-orders-of-magnitude range of protein abundances in the cell should leave imprints on extant protein structures, a prediction that is supported by our structural analysis of the yeast proteome.2013-01-01T00:00:00Z2013 Feb2025-04-04T10:11:59.034Z2019-03-27T01:04:28ZS-EPMC35664492344292410.1016/j.bpj.2012.11.3838