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Research Article
Arthur T. Kopylov
V.N. Orekhovich Institute of Biomedical Chemistry
Corresponding Author
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Post-translational processing leads to conformational changes in protein structure that modulate molecular functions and change the signature of metabolic transformations and immune responses. Some post-translational modifications (PTMs), such as phosphorylation and acetylation, are strongly related to oncogenic processes and malignancy. This study investigated a PTM pattern in patients with gender-specific ovarian or breast cancer. Proteomic profiling and analysis of cancer-specific PTM patterns were performed using high-resolution UPLC-MS/MS. Structural analysis, topology, and stability of PTMs associated with sex-specific cancers were analyzed using molecular dynamics modeling. We identified highly specific PTMs, of which 12 modified peptides from eight distinct proteins derived from patients with ovarian cancer and 6 peptides of three proteins favored patients from the group with breast cancer. We found that all defined PTMs were localized in the compact and stable structural motifs exposed outside the solvent environment. PTMs increase the solvent-accessible surface area of the modified moiety and its active environment. The observed conformational changes are still inadequate to activate the structural degradation and enhance protein elimination/clearance; however, it is sufficient for the significant modulation of protein activity.
Keywords
breast cancer, ovarian cancer, post-translational modifications, protein structural motifs, active environment of amino acid, molecular dynamics, ultrahigh-resolution mass spectrometry
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No competing interests reported.
This is a list of supplementary files associated with this preprint. Click to download.
- SupplementaryMaterials.pdf
Supplementary Materials Supplementary Materials Collection contains information about plasma-based differentially expressed proteins (DEP), detailed results of molecular dynamics simulation and molecular geometry features; distribution of the identified PTMs amongst studied phenotypes and rules for qualification of secondary structures considered in the study.
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Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 17 May, 2021
No community comments so far
Editorial decision: Major revision
On 14 Jun, 2021
Reviews received
Received 11 Jun, 2021
Reviewers agreed
On 26 May, 2021
Reviewers invited
Invitations sent on 25 May, 2021
Editor assigned
On 25 May, 2021
Editor invited
On 17 May, 2021
Submission checks complete
On 11 May, 2021
First submitted
On 07 May, 2021
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Subject Areas
Mathematical and Theoretical Biology
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A new preprint design is coming!
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This preprint is under consideration at Scientific Reports. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research Article
Arthur T. Kopylov
V.N. Orekhovich Institute of Biomedical Chemistry
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 17 May, 2021
No community comments so far
Editorial decision: Major revision
On 14 Jun, 2021
Reviews received
Received 11 Jun, 2021
Reviewers agreed
On 26 May, 2021
Reviewers invited
Invitations sent on 25 May, 2021
Editor assigned
On 25 May, 2021
Editor invited
On 17 May, 2021
Submission checks complete
On 11 May, 2021
First submitted
On 07 May, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Mathematical and Theoretical Biology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Post-translational processing leads to conformational changes in protein structure that modulate molecular functions and change the signature of metabolic transformations and immune responses. Some post-translational modifications (PTMs), such as phosphorylation and acetylation, are strongly related to oncogenic processes and malignancy. This study investigated a PTM pattern in patients with gender-specific ovarian or breast cancer. Proteomic profiling and analysis of cancer-specific PTM patterns were performed using high-resolution UPLC-MS/MS. Structural analysis, topology, and stability of PTMs associated with sex-specific cancers were analyzed using molecular dynamics modeling. We identified highly specific PTMs, of which 12 modified peptides from eight distinct proteins derived from patients with ovarian cancer and 6 peptides of three proteins favored patients from the group with breast cancer. We found that all defined PTMs were localized in the compact and stable structural motifs exposed outside the solvent environment. PTMs increase the solvent-accessible surface area of the modified moiety and its active environment. The observed conformational changes are still inadequate to activate the structural degradation and enhance protein elimination/clearance; however, it is sufficient for the significant modulation of protein activity.
Figure 1
Figure 2
Figure 3
Figure 4
No competing interests reported.
This is a list of supplementary files associated with this preprint. Click to download.
- SupplementaryMaterials.pdf
Supplementary Materials Supplementary Materials Collection contains information about plasma-based differentially expressed proteins (DEP), detailed results of molecular dynamics simulation and molecular geometry features; distribution of the identified PTMs amongst studied phenotypes and rules for qualification of secondary structures considered in the study.
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