Introduction Protein Domains Research Question PTM Tracker: A System For Determining Method Trends Of PTM Modification Sites Relative To Results Thanks To Protein domains Oliver Bonham-Carter Presented by Janyl Jumadinova 20 May 2016 1 / 27
Evolutionarily Conserved Across Biology Similar genetic material across diverse organisms Introduction Protein Domains Research Question Method Results Thanks To Copies of genes: common gene material DNA makes proteins having similar biological functions 1 / 27
Evolutionarily Conserved Across Biology Central dogma of biology Introduction Protein Domains Research Question Method Results Thanks To DNA creates RNA to synthesize proteins 2 / 27
Evolutionarily Conserved Across Biology The same genetic material across organisms Introduction Protein Domains Research Question Method Results Thanks To Sharing common DNA gives common proteins 3 / 27
Protein Domain Architectures Introduction Protein Domains Research Question Method Results Thanks To 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). 4 / 27
Domains May Be Found In Diverse Protein Introduction Protein Domains Research Question Method Results Thanks To Domain “copies” may be found in diverse proteins Protein domains activated by post-translational modification mechanisms 5 / 27
PTMs: A Step In Protein Biosynthesis A biochemical modification Introduction Protein Domains Research Question Method Results Thanks To PTMs refer to the covalent and generally enzymatic modification of proteins during or after protein biosynthesis. Two protein sequences having different functionalities. Mature proteins are structurally appropriate for functional tasks. 6 / 27
What Are Post-translational Modifications? Changing the structural and functional rules Introduction Protein Domains Research Question Method Results Thanks To PTMs refer to the covalent and generally enzymatic modification by biosynthesis of protein material to enable specific functionality 7 / 27
Some Common Types of PTMs The quick-addition of a group for conformational change and function. Introduction Protein Domains Research Question Method Results Thanks To 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
Research Questions Introduction Protein Domains Research Question Method Results Thanks To Domains are initiated by PTMs at specific Modification Sites (MSs) What parts of this mechanism are conserved across diverse organisms? What can we learn from these patterns to investigate health issues? 9 / 27
Two Types Of Studies Domains associated with PTMs Introduction Protein Domains Research Question An Organism-centric study : All protein domains associated Method with a specific type of organism are selected for study Results A Domain-centric study : A particular protein domain type is Thanks To selected for study across all the data where is found (in any type of 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. 10 / 27
Organism-Centric Study Three Types of Criteria Introduction Protein Domains Research Question Method Results Thanks To { 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 11 / 27
General Overview - Organism Centric Study MSs before domains Introduction Protein Domains Research Question Method Results Organism- Centric Domain-Centric Conclusions Thanks To 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 12 / 27
Dist. Between Domains and MSs: Before Regions Introduction Protein Domains Research Question Method Results Organism- Centric Domain-Centric Conclusions Thanks To MSs occurring Before domains. We have data for MSs occurring Inside and After domains 13 / 27
MSs Upstream of Org-Centric Domains, Acetylation Homo Sapiens (Human) Introduction Protein Domains Research Question Method Results Organism- Centric Domain-Centric Conclusions Thanks To 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 14 / 27
MSs Upstream of Org-Centric Domains, Acetylation Canis Familiaris (Dog) Introduction Protein Domains Research Question Method Results Organism- Centric Domain-Centric Conclusions Thanks To 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 15 / 27
MSs Upstream of Org-Centric Domains, Acetylation Comparison: Human (top) and Dog (bottom) Introduction Protein Domains Research Question Method Results Organism- Centric Domain-Centric Conclusions Thanks To 16 / 27
MSs Within Org-Centric Domains, Acetylation Homo Sapiens (Human) Introduction Protein Domains Research Question Method Results Organism- Centric Domain-Centric Conclusions Thanks To 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 17 / 27
MSs Within Org-Centric Domains, Acetylation Canis Familiaris (Dog) Introduction Protein Domains Research Question Method Results Organism- Centric Domain-Centric Conclusions Thanks To 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 18 / 27
MSs Within Org-Centric Domains, Acetylation Comparison: Human (top) and Dog (bottom) Introduction Protein Domains Research Question Method Results Organism- Centric Domain-Centric Conclusions Thanks To 19 / 27
General Overview - Domain-Centric Study Collect MSs, and domain beginning and ending locations in each protein Introduction Protein Domains Research Question Method Results Organism- Centric Domain-Centric Conclusions Thanks To 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 20 / 27
Reading The Plots Introduction Protein Domains Research Question Method Results Organism- Centric Domain-Centric Conclusions Thanks To All measurements are proportal distances and can be compared across all protein samples. 21 / 27
Acetylation, Domain-Centric: jmjn At least 37 domains found in data Introduction Protein Domains Research Question Method Results Organism- Centric Domain-Centric Conclusions Thanks To 22 / 27
Acetylation, Domain-Centric: jmjc At least 114 domains found in data Introduction Protein Domains Research Question Method Results Organism- Centric Domain-Centric Conclusions Thanks To 23 / 27
General Observations Introduction Protein Domains Organism-Centric Analysis Research Question Organismal protein samples: Many conserved (typical) distances Method between MS neighbourhoods occurring before , inside and after Results domain regions Organism- Centric Many organism-specific mechanisms were found Domain-Centric Conclusions Unique MS neighbourhoods between related organisms Thanks To 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 24 / 27
Conclusions Introduction Protein Domains Research From our data Question Evidence for specific locations placement of MSs relative to Method domains, by organism and domain-centric analysis Results Organism- These common distances may also describe protein folding Centric Domain-Centric requirements Conclusions Thanks To 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 25 / 27
Introduction Protein Domains Research Question Method Thank You! Questions? Results Thanks To obonhamcarter@unomaha.edu IS&T Bioinformatics http://bioinformatics.ist.unomaha.edu/ 26 / 27
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