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Structural and functional analysis of “non-smelly” proteins

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Abstract

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.

Highlights

  • Cysteine-depleted proteins are abundant in all domains of life.

  • Prokaryotes are significantly enriched in cysteine-depleted proteins compared to eukaryotes.

  • Only about 0.05% of proteins are depleted in aromatic residues and cysteine.

  • Proteins depleted in aromatic residues and cysteine have high levels of intrinsic disorder.

  • Organisms with higher levels of cysteine-depleted proteins have higher levels of the intrinsic disorder.

  • “Non-smelly” proteins are involved in translation, transcription, nucleosome assembly, protein folding, and transmembrane transport functions.

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Acknowledgements

This research was supported in part by the Qimonda Endowment and the National Science Foundation Grant 1617369 to Lukasz Kurgan.

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Authors and Affiliations

  1. Department of Electrical and Computer Engineering, University of Alberta, Edmonton, Canada

    Jing Yan

  2. Department of Electrical Engineering and Computer Science, University of Missouri, Columbia, USA

    Jianlin Cheng

  3. Department of Computer Science, Virginia Commonwealth University, 401 West Main Street, Room E4225, Richmond, VA, 23284, USA

    Lukasz Kurgan

  4. Department of Molecular Medicine and USF Health Byrd Alzheimer’s Research Institute, Morsani College of Medicine, University of South Florida, 12901 Bruce B. Downs Blvd., MDC07, Tampa, FL, 33612, USA

    Vladimir N. Uversky

  5. Protein Research Group, Institute for Biological Instrumentation of the Russian Academy of Sciences, 142290, Pushchino, Moscow Region, Russia

    Vladimir N. Uversky

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  1. Jing Yan
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Yan, J., Cheng, J., Kurgan, L. et al. Structural and functional analysis of “non-smelly” proteins. Cell. Mol. Life Sci. 77, 2423–2440 (2020). https://doi.org/10.1007/s00018-019-03292-1

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