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Structural and functional analysis of “non-smelly” proteins

  • Jing Yan
  • Jianlin Cheng
  • Lukasz KurganEmail author
  • Vladimir N. UverskyEmail author
Original Article

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.

Keywords

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

Notes

Acknowledgements

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

Compliance with ethical standards

Conflict of interest

The authors have declared no conflict of interest.

Supplementary material

18_2019_3292_MOESM1_ESM.pdf (557 kb)
Supplementary material 1 (PDF 557 kb)

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Electrical and Computer EngineeringUniversity of AlbertaEdmontonCanada
  2. 2.Department of Electrical Engineering and Computer ScienceUniversity of MissouriColumbiaUSA
  3. 3.Department of Computer ScienceVirginia Commonwealth UniversityRichmondUSA
  4. 4.Department of Molecular Medicine and USF Health Byrd Alzheimer’s Research Institute, Morsani College of MedicineUniversity of South FloridaTampaUSA
  5. 5.Protein Research GroupInstitute for Biological Instrumentation of the Russian Academy of SciencesPushchinoRussia

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