Structural and Functional Analysis of “non-smelly” Proteins

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Intrinsically disordered proteins, Cysteine-depleted proteins, Nucleic acid-binding proteins, Proteins depleted in cysteine and aromatic residues, Protein structure, Protein function

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Cysteine and aromatic residues are major structure-promoting residues. We assessed the abundance, structural coverage, and functional characteristics of the “non-smelly” proteins, i.e., proteins that do not contain cysteine residues (C-depleted) or cysteine and aromatic residues (CFYWH-depleted), across 817 proteomes from all domains of life. The analysis revealed that although these proteomes contained significant levels of the C-depleted proteins, with prokaryotes being significantly more enriched in such proteins than eukaryotes, the CFYWH-depleted proteins were relatively rare, accounting for about 0.05% of proteomes. Furthermore, CFYWH-depleted proteins were virtually never found in PDB. Depletion in cysteine and in aromatic residues was associated with the substantially increased intrinsic disorder levels across all domains of life. Archaeal and eukaryotic organisms with higher levels of the C-depleted proteins were shown to have higher levels of the intrinsic disorder and lower levels of structural coverage. We also showed that the “non-smelly” proteins typically did not independently fold into monomeric structures, and instead, they fold by interacting with nucleic acids as constituents of the ribosome and nucleosome complexes. They were shown to be involved in translation, transcription, nucleosome assembly, transmembrane transport, and protein folding functions, all of which are known to be associated with the intrinsic disorder. Our data suggested that, in general, structure of monomeric proteins is crucially dependent on the presence of cysteine and aromatic residues.

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Cellular and Molecular Life Sciences, v. 77, p. 2423-2440