This web page was produced as an assignment for Genetics 564, an undergraduate course at UW-Madison.
Protein Domains
Protein domains are protein units (small segments) that have been conserved throughout evolution and have a specific structure and function [1,2]. If a protein has only one domain, the function and structure of that protein is often dictated by the function of that domain. Proteins can also consist of multiple domains. In this situation, the function and overall structure of the protein often becomes a combination of all the domains [1]. Domains that have a common ancestor can be grouped into superfamilies [1]. While domains are structural and functional units, motifs are the actual sequence of the protein.
TOP3β Protein Domains
Below is a figure comparing the domains of the TOP3β homologs. These domains were found using SMART (a Simple Modular Architecture Research Tool), an online database of domains. SMART also provides information about domain function, domain structure, and functionally important amino acids within the protein domain [3]. The protein sequence was entered into the program for each of the species below while in 'normal' mode.* By clicking on the three domains in the resultant image, I was able to collect information such as how many amino acids long the domain was, its location within the protein, and the domain function.
*SMART can be run in two modes, normal or genomic. In the normal mode, the database proteome information from three different protein databases: Swiss-Prot, SP-TrEMBL, and Ensembl. In genomic mode, only proteins of completely sequenced genomes are used and this data come from only two databases: Ensembl and Swiss-Prot [4]. A proteome is the complete set of proteins within the organism, as genome is to genes.
Analyzing the TOP3β Domains
The TOPRIM (topoisomerase-primase) domain is a highly conserved domain among topoisomerase, primases, nucleases, and bacterial DNA repair proteins [5]. It was roughly (give or take an amino acid or two) 135 amino acids in all the homologs above. The TOP1Bc and TOP1Ac domains are ATP-binding domains that are involved in the DNA binding and topological activity of the protein [6].
It can be seen from the figure above that the TOP3β protein is highly conserved as the domains are all in nearly the exact same position. The proteins and the three domains are also all nearly the exact same length. This finding is not surprising as this protein has a very important function within the cell--making the DNA accessible from processes such as DNA replication.
It can be seen from the figure above that the TOP3β protein is highly conserved as the domains are all in nearly the exact same position. The proteins and the three domains are also all nearly the exact same length. This finding is not surprising as this protein has a very important function within the cell--making the DNA accessible from processes such as DNA replication.
References
[1]. Vogel, C. et. al. (2004). Structure, Function, and Evolution of Multidomain Proteins. Current Opinion in Structural Biology, 14:208–216. DOI 10.1016/j.sbi.2004.03.011 http://www.nyu.edu/projects/vogel/Reprints/Vogel_COSB04.pdf
[2]. EMBL-EBI. What are protein domains? retrieved Apr. 10, 2014. http://www.ebi.ac.uk/training/online/course/introduction-protein-classification-ebi/protein-classification/what-are-protein-domains
[3]. SMART. Overview. retrieved Apr. 10, 2014. http://smart.embl-heidelberg.de/help/smart_about.shtml
[4]. SMART. Select your default SMART mode. retrieved Apr. 10, 2014. http://smart.embl-heidelberg.de/smart/change_mode.pl
[5]. Aravind, L. Leipe, DD. Koonin, EV. (1998). Toprim--a conserved catalytic domain in type IA and II topoisomerases, DnaG-type primases, OLD family nucleases and RecR proteins. Nucleic Acids Res. 15;26(18):4205-13. PMID: 9722641 http://www.ncbi.nlm.nih.gov/pubmed/9722641
[6]. SMART. Domains within Homo sapiens protein TOP3B_Human. retrieved Apr. 10, 2014. http://smart.embl-heidelberg.de/smart/show_motifs.pl
[2]. EMBL-EBI. What are protein domains? retrieved Apr. 10, 2014. http://www.ebi.ac.uk/training/online/course/introduction-protein-classification-ebi/protein-classification/what-are-protein-domains
[3]. SMART. Overview. retrieved Apr. 10, 2014. http://smart.embl-heidelberg.de/help/smart_about.shtml
[4]. SMART. Select your default SMART mode. retrieved Apr. 10, 2014. http://smart.embl-heidelberg.de/smart/change_mode.pl
[5]. Aravind, L. Leipe, DD. Koonin, EV. (1998). Toprim--a conserved catalytic domain in type IA and II topoisomerases, DnaG-type primases, OLD family nucleases and RecR proteins. Nucleic Acids Res. 15;26(18):4205-13. PMID: 9722641 http://www.ncbi.nlm.nih.gov/pubmed/9722641
[6]. SMART. Domains within Homo sapiens protein TOP3B_Human. retrieved Apr. 10, 2014. http://smart.embl-heidelberg.de/smart/show_motifs.pl