PTM Tracker: A System For Determining Method Trends Of PTM - - PowerPoint PPT Presentation

Introduction Protein Domains Research Question Method Results Thanks To

PTM Tracker: A System For Determining Trends Of PTM Modification Sites Relative To Protein domains

Oliver Bonham-Carter Presented by Janyl Jumadinova 20 May 2016

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Evolutionarily Conserved Across Biology

Similar genetic material across diverse organisms

Copies of genes: common gene material DNA makes proteins having similar biological functions

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Evolutionarily Conserved Across Biology

Central dogma of biology

DNA creates RNA to synthesize proteins

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Introduction Protein Domains Research Question Method Results Thanks To

Evolutionarily Conserved Across Biology

The same genetic material across organisms

Sharing common DNA gives common proteins

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Protein Domain Architectures

Protein Domains: conserved parts of a protein sequence and structure, able to evolve, function, and exist independently of the rest of the protein chain Pyruvate kinase, a protein with three domains (see different colours).

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Domains May Be Found In Diverse Protein

Domain “copies” may be found in diverse proteins Protein domains activated by post-translational modification mechanisms

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PTMs: A Step In Protein Biosynthesis

A biochemical modification

PTMs refer to the covalent and generally enzymatic modification

• f proteins during or after protein biosynthesis.

Two protein sequences having different functionalities. Mature proteins are structurally appropriate for functional tasks.

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What Are Post-translational Modifications?

Changing the structural and functional rules

PTMs refer to the covalent and generally enzymatic modification by biosynthesis of protein material to enable specific functionality

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Some Common Types of PTMs

The quick-addition of a group for conformational change and function.

Although we could use any PTM, we study acetylation thanks to the abundance of data existing in the literature

Deribe, et al “Post-translational modifications in signal integration.” Nature structural & molecular biology 17.6 (2010): 666-672. http://www.nature.com/nsmb/journal/v17/n6/fig_tab/nsmb.1842_F1.html 8 / 27

Introduction Protein Domains Research Question Method Results Thanks To

Research Questions

Domains are initiated by PTMs at specific Modification Sites (MSs) What parts of this mechanism are conserved across diverse

• rganisms?

What can we learn from these patterns to investigate health issues?

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Two Types Of Studies

Domains associated with PTMs

An Organism-centric study: All protein domains associated with a specific type of organism are selected for study A Domain-centric study: A particular protein domain type is selected for study across all the data where is found (in any type

• f organism)

We study all protein domains involved with acetylation and their associated MSs. We are measuring the distances between these MSs and their associated protein domains.

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Organism-Centric Study

Three Types of Criteria

{A,K,N} are the amino acid modification sites of acetylation for the domain (yellow) Blue regions: Before MSs and upstream of domains Yellow regions: Inside MSs and within domains Green regions: After : MSs and downstream of domains

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Organism- Centric Domain-Centric Conclusions

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General Overview - Organism Centric Study

MSs before domains

Protein records from UniProt; parsed by organism for PTM, MS and domain information. Proportional distances (for cross comp.) of MS to its domain MSs neighbourhoods: clusters of MSs common locations Neighbourhoods are plotted

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Organism- Centric Domain-Centric Conclusions

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• Dist. Between Domains and MSs: Before Regions

MSs occurring Before domains. We have data for MSs occurring Inside and After domains

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Organism- Centric Domain-Centric Conclusions

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MSs Upstream of Org-Centric Domains, Acetylation

Homo Sapiens (Human)

The x-axis represents the location of the MS neighbourhoods (green) The y-axis describes the number of times that this same location was observed for the element across the samples MSs are generally found just outside the domain

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Organism- Centric Domain-Centric Conclusions

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MSs Upstream of Org-Centric Domains, Acetylation

Canis Familiaris (Dog)

The x-axis represents the location of the MS neighbourhoods (green) The y-axis describes the number of times that this same location was observed for the element across the samples MSs are generally found just outside the domain but are also in scattered neighbourhoods

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Organism- Centric Domain-Centric Conclusions

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MSs Upstream of Org-Centric Domains, Acetylation

Comparison: Human (top) and Dog (bottom)

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Organism- Centric Domain-Centric Conclusions

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MSs Within Org-Centric Domains, Acetylation

Homo Sapiens (Human)

The x-axis represents the location of the MS neighbourhoods (green) The y-axis describes the number of times that this same location was observed for the element across the samples MSs are generally found in many scattered neighbourhoods throughout domains

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Organism- Centric Domain-Centric Conclusions

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MSs Within Org-Centric Domains, Acetylation

Canis Familiaris (Dog)

The x-axis represents the location of the MS neighbourhoods (green) The y-axis describes the number of times that this same location was observed for the element across the samples MSs are generally found in scattered isolated neighbourhoods throughout domains

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Organism- Centric Domain-Centric Conclusions

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MSs Within Org-Centric Domains, Acetylation

Comparison: Human (top) and Dog (bottom)

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Organism- Centric Domain-Centric Conclusions

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General Overview - Domain-Centric Study

Collect MSs, and domain beginning and ending locations in each protein

Protein records from UniProt; parsed for specific type of protein domain. Obtain MSs and domain start and stop (proportional) locations MSs neighbourhoods: clusters of MSs common locations Neighbourhoods are plotted

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Organism- Centric Domain-Centric Conclusions

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Reading The Plots

All measurements are proportal distances and can be compared across all protein samples.

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Organism- Centric Domain-Centric Conclusions

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Acetylation, Domain-Centric: jmjn

At least 37 domains found in data

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Organism- Centric Domain-Centric Conclusions

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Acetylation, Domain-Centric: jmjc

At least 114 domains found in data

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Organism- Centric Domain-Centric Conclusions

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General Observations

Organism-Centric Analysis

Organismal protein samples: Many conserved (typical) distances between MS neighbourhoods occurring before, inside and after domain regions Many organism-specific mechanisms were found Unique MS neighbourhoods between related organisms

Domain-Centric Analysis

Many specific domains where PTM MSs were consistently found at specific locations (before) domains. Rare to find domains having its MSs at both before and after positions

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Conclusions

From our data

Evidence for specific locations placement of MSs relative to domains, by organism and domain-centric analysis These common distances may also describe protein folding requirements PTM-Tracker has the potential to help us understand what normal protein-PTM interactions should look like so that we can identify abnormal conditions This tool allows us to identify the outliers which could become medical ailments concerning protein health

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Thank You! Questions?

• bonhamcarter@unomaha.edu

IS&T Bioinformatics http://bioinformatics.ist.unomaha.edu/

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Amino Acid Composition To Explain MS Bias?

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