Background: Eukaryotic cells contain a huge variety of internally specialized subcellular compartments.Stoichiogenomics aims to reveal patterns of elements usage in biological macromolecules. However, thestoichiogenomic characteristics and how they adapt to various subcellular microenvironments are stillunknown.

Results: Here we first updated the definition of stoichiogenomics. Then we applied it to subcellular research, anddetected distinctive nitrogen content of nuclear and hydrogen, sulfur content of extracellular proteomes. Specially,we found that acidic amino acids (AAs) content of cytoskeletal proteins is the highest. The increased charged AAs aremainly caused by the eukaryotic originated cytoskeletal proteins. Functional subdivision of the cytoskeleton showedthat activation, binding/association, and complexes are the three largest functional categories. Electrostatic interactionanalysis showed an increased electrostatic interaction between both primary sequences and PPI interfaces of 3Dstructures, in the cytoskeleton.

Conclusions: This study creates a blueprint of subcellular stoichiogenomic characteristics, and explains that chargedAAs of the cytoskeleton increased greatly in evolution, which offer material basis for the eukaryotic cytoskeletalproteins to act in two ways of electrostatic interactions, and further perform their activation, binding/association andcomplex formation.