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Comparative structural analysis of Borreliella spp. virulent factors focusing on their surface topology conservation
Zdrha, Alois ; Drbal, Karel (advisor) ; Nunvář, Jaroslav (referee)
Gram-negative bacteria of genus Borreliella cause the nowadays spreading illness Lyme borreliosis. However, their classification as gram-negative bacteria is rather mislea- ding because they differ in their complex genome, pathogenic adaptation to their hosts and composition of their outer membrane. One species of borreliella can harbour up to 23 variable plasmids and one conserved chromosome and they still lack many crucial proteins needed for synthesis of key compounds. Hence, they have to obtain these compounds from the host. However, in order for borreliella to utilise the metabolic processes of the host, it has to first survive its immune response. Therefore borreliella contains many virulent factors including highly variable surface lipoproteins. The variability is a major obstacle to overcome when using their surface epitopes for detection and vaccine development because most of the dominant antigenic epitopes of borreliella are usually parts of the most variable regions of the lipoproteins. Nowadays, we can use many different algorithms which determine evolutionary conserved epitopes based on analysis of sequences of given lipoprotein, in order to find suitable targets for antibodies. In general, conserved epitopes are more suitable for vaccines, whereas more variable epitopes are better...
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Structure- and sequence-based identification of functionally important amino acids in a protein family
Peclinovská, Iveta ; Novotný, Marian (advisor) ; Pleskot, Roman (referee)
A group of small GTPases consist of over twenty protein families in the super class P-loop. It has a very diverse cell functions. Small GTPases regulate the formation of vesicular follicles, cytoskeleton and nuclear transport. They participate also on cell proliferation and signaling. The aim of my work is to find important amino acids that define family and distinguish each other. I focus on families Arf, Rab, Ran, Ras and Rho. At the Rho family I am also devoted to classes Rho, Rac and Cdc42. Amino acids are identified using bioinformatic programs selected Consurf and Sca5. The objective is also to test P2RANK specialized tool developed at the Charles University in Prague that predict ligand binding sites from protein structure in different families. Founding amino acids can have a big role in the functional divergence of individual families and classes of small GTPases and can be the basis for future study example for the proliferation of cancerous cells. 1.1 Keywords Powered by TCPDF (www.tcpdf.org)
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Are there any sequence determinants of functional divergence of GTPases?
Kraus, Ondřej ; Novotný, Marian (advisor) ; Potocký, Martin (referee)
Small GTPases are important proteins that affect many cellular processes. In my work I compare the five most important protein families of small GTPases - Arf, Rab, Ran, Ras and Rho to identify amino acids responsible for major functional differences between different protein families. To compare them, I have used the structural data from the PDB database and sequences from the UniProt database. I have discovered previously undescribed groups of amino acids specific for each protein family of small GTPases with the help of programs ConSurf and Sca5. I also carried out a pilot study of the applicability of B-factors as indicators of bond strength in the protein structure on the example of small GTPases. The first results are not entirely conclusive, but they do not exclude the applicability of B-factors as indicators of bond strength either. Powered by TCPDF (www.tcpdf.org)
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