There are 4 buttons for start script under the applet: Protein-Ligand, Hydrophilic, Hydrogene, Salt Bridges. Each script has several visualisations, so press "Resume" to move between them. Button "Rotate" and " Rotate off" start and stop the rotation of the Macromolecule. 1. Protein-protein Salt bridges
2. Protein – ligand First, we selected chains of one protein and with the help of command “within” saw atoms not farther than 2.5 A. There were found only two atoms (one at the distance of 2.42A, the other at the distance of 2,47A). This led us to the conclusion that there is no covalent bond between proteins. We also noticed that there is an interaction between ARG and ASP - salt bond. In chemistry, a salt bridge is a combination of two noncovalent interactions: hydrogen bonding and electrostatic interactions. Usually they contribute stability of tertiary structure of proteins. The salt bridge most often arises from the anionic carboxylate (RCOO-) of either aspartic acid or glutamic acid and the cationic ammonium (RNH3+) from lysine or the guanidinium (RNHC(NH2)2+) of arginine. The distance between the residues participating in the salt bridge is also cited as being important. The distance required is less than 4 A (400 pm) We suppose that in our case salt bonds between flagellin and TLR5 are needed to amplify the contact that will not collapse under external influence (such as thermal, for example). Hydrofobic interactions In order to fold into energetically favorable conformation hydrophobic radicals of aminoacids(such as valine, leucine, isoleucine, proline, methionine and phenylalanine) Strive to unite into a globular structure in the center of the protein. Thus, hydrophobic interaction, and van der Waals interactions between closely adjacent to each other atoms appear. As a result, they form the protein globule inside the protein called hydrophobic core. Hydrophobical interactions must play a significant role in our complex, because TLR - is trasmembrane protein. The process of recognision and visualisation of hydrophobic cores can briefle be outlined as: 1). With the usage of CluD we found all cores in our complex. Next, we selected 4 biggest cores and analysed them: 1). Core 1 - atoms, chain A of TLR 2). Core 2 - atoms, chains B and D 3). Core 3 - atoms, chains A and C 4). Core 25 - atoms, chain B Than we wrote a script to visualize them We can see, that huge hydrophobic cores form the structure of our complex. Mostly they are parts of TLR (cores 1 and 25 totally, and cores 2 and 3 bond chains of TLR and flagellin). So, our supposions were proved. And hydrophobic interactions not only form the structure of TLR, but also bond two proteins in the complex. Hydrogen bonds Analysis of the structure of our complex (the description in PDB file) revealed the presence of two types of ligands: NAG and PG4. The first step of ligand-protein bonds’ search was to determine the location of the hydrophobic core and the possibility of hydrophobic bonds formation. We found out, that it is impossible because of large distance between ligands and nucleus. The next step was to look through all atoms within a radius of 3.5 angstroms, which could potentially form hydrogen bonds. We managed to find such bond, moreover we found out, that PG4 molecules are located within a radius of 2.9 angstroms, near the positively charged amino acids (His, and Arg). Thus, we could suggest, that the formation of a negative charge in the ligand takes place, so as the formation of a salt bridge. The exploration of NAG ligands’ surroundings showed, that there are distinct covalent bonds between NAG and A and B chains of TLR 5 (mostly with Asn). To see the visualization, press the button “Protein-ligand”.
The most interesting detail about protein-ligand interactions is its biological sense. All ligands are binded with A and B chains of TLR5, so we suppose, that ligands (as PAMPs) could be coactivators of the receptor.
During the research, we discovered and described different types of protein- protein interactions and protein- ligands interactions. In prot-prot there are hydrophobic bonds, salt bridges and hydrogen bonds. Covalent, hydrogen and salt bonds – are main types of bonds, which take place in protein-ligand interactions. Moreover, we found out that both NAG and PG4 are bonded only with A and B chains of Toll-like receptor 5.
We found information about our complex, its macromolecules and ligands (functions, structure, nomenclature). Also we understood how innate inmunity and adaptive immunity are connected and comprehensed the scheme of this mechanism.
1. Maria Selifanova: discovered and described hydrophobic cores and hydrophobic interactions, discribed hydrogene bonds, author of the script “Hydrophobic interactions”. Author of the text, author of html code and web-page design.
2. Eugenia Elisarova: found the protein complex to explore in PDB, discovered and described all protein-ligand interactions, specialist at bonds’ searching, the author of the script “Protein-Ligand interactions” and "Hydrogene". Script editor. 3. Maria Gurileva – found information about structure, function and nomenclature of macromolecules in our complex, discovered and described salt bridges, the author of the script “Salt bridges”, translated the text into Russian. Authors thank FBB student Zaira Seferbekova for editing the English version of the article.
1.http://www.rcsb.org/pdb/home/home.do
2. http://www.rcsb.org/pdb/explore/explore.do?structureId=5GY2 3.http://www.nobelprize.org/nobel_prizes/medicine/laureates/2011/ 4.http://www.rcsb.org/pdb/explore/explore.do?structureId=5GY2 5. http://instanet.club/page/video/toll-like-receptor 6. https://en.wikipedia.org/wiki/Flagellin 7. http://microbeonline.com/bacterial-flagella-structure-importance-and-examples-of-flagellated-bacteria/ 8. https://www3.rcsb.org/ligand/NAG 9. https://www3.rcsb.org/ligand/PG4 10. https://en.wikipedia.org/wiki/Salt_bridge_(protein_and_supramolecular) | |||||||||||||||||
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