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User:Ketan Mathavan/Sandbox 1: Difference between revisions

New page: frame|Bacterial chemotaxis receptor Many bacteria can "smell" their surroundings and "choose" where to go. They detect molecules such as amino acids or ...
 
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[[Image:intactModelLargeText.jpg|frame|Bacterial chemotaxis receptor]]
<Structure load='3SPA' size='370' frame='true' align='right' caption='Human mitochondrial RNA polymerase (PDB: 3SPA) scene='Insert optional scene name here' />


Many bacteria can "smell" their surroundings and "choose" where to go. They detect molecules such as amino acids or sugars using receptors that bind these molecules and transmit a signal into the cell. This signal controls several proteins which ultimately control the motors that rotate the flagella to cause the cell to either continue swimming or to tumble. When an attractant molecule binds, it signals: "Things look good, keep swimming!" The opposite signal occurs when bacteria sense decreasing concentrations of attractant molecules: "Time to tumble and try a new swimming direction."
One of the [[CBI Molecules]] being studied in the  [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].


=== Transcription and the human mitochondrial RNA polymerase ===


A bacterial chemotaxis receptor is an unusually long alpha-helical structure. The attractant molecule (the ligand) binds near the top of this picture and sends a signal across the membrane into the cell to control proteins that bind near the bottom. This is a model of the structure of the receptor based on experimental structures of pieces of related proteins.
The central dogma of biology in which genetic information is transferred from DNA to RNA, and subsequently into protein, is fundamental to life. A key player in this process is the DNA-dependent RNA polymerase. RNA polymerase produces RNA in the presence of a DNA template under tight control by the cell. In the Martin lab, our goal is to elucidate the energetics and thermodynamics of this complicated process. As a model, we use T7 bacteriophage RNA polymerase (PDB:1QLN). This single-subunit polymerase can transcribe DNA without assistance from other proteins, making it an ideal model to understand transcription. Likewise, it is representative of all other known RNA polymerases in that it initiates at unique positions along the DNA, undergoes abortive cycling, transitions to a stable elongation complex, and terminates transcription at specific sequences.  


{{Clear}}
Related to the T7 RNA polymerase is the human mitochondrial RNA polymerase <scene name='User:Lynmarie_K_Thompson/Sandbox_1/Loadedfrompdb/4'> (PDB: 3SPA)</scene>. Recent crystallization of this enzyme by [http://www.ncbi.nlm.nih.gov/pubmed/21947009 Temiakov et al.] has revealed structural similarity between the two polymerases. The <font color =gray> C-terminal </font> <scene name='User:Lynmarie_K_Thompson/Sandbox_1/Loadedfrompdb/4'>domain</scene> contains the active site for RNA synthesis. The <font color=magenta> N-terminal </font> <scene name='User:Lynmarie_K_Thompson/Sandbox_1/Loadedfrompdb/4'> domain, </scene>(NTD) contains the promoter-binding domain (PBD) essential for DNA binding and start site specificity. Key structures of the NTD include the <font color=red> specificity </font> <scene name='User:Lynmarie_K_Thompson/Sandbox_1/Loadedfrompdb/4'>loop</scene>, <font color=orange> intercalating </font> <scene name='User:Lynmarie_K_Thompson/Sandbox_1/Loadedfrompdb/4'>loop</scene> , and <font color=blue> AT-recognition </font> <scene name='User:Lynmarie_K_Thompson/Sandbox_1/Loadedfrompdb/4'>loop</scene>.
<applet load='1wat' size='[450,338]' frame='true' align='right'
caption='Aspartate receptor ligand binding domain (1wat)' scene='User:Lynmarie_K_Thompson/Sandbox_1/Loadedfrompdb/4'/>


=== Ligand-binding domain ===
One very big difference between the two polymerases is in the form of two transcription factors, TFB2M and TFAM. Human mtRNA polymerase requires these two proteins for binding and melting of promoter DNA. TFAM binds 15-40 base pairs upstream while TFB2M binds more proximal to the transcription start site (1-3). The requirement of these transcription factors coupled with the discrepancy of PBD orientation between T7 (Fig. 2; salmon) and human mtRNA polymerase (Fig. 2; grey) suggests a role in enzyme remodeling for the transcription factors, namely, TFB2M. By studying the structural changes and differences between the two polymerases, we can better under the energetics that governed transcription.


== References ==


#Ekstrand, M. I. Mitochondrial transcription factor A regulates mtDNA copy number in mammals. Hum. Mol. Genet. 13, 935-944 (2004). [http://www.ncbi.nlm.nih.gov/pubmed/15016765 Pubmed]
#Dairaghi, D. J., Shadel, G. S., Clayton, D. A. Human mitochondrial transcription factor A and promoter spacing integrity are required for transcription initiation. Biochim. Biophys. Acta 1271, 127-134 (1995). [http://www.ncbi.nlm.nih.gov/pubmed/7599198 Pubmed]
#Sologub, M., Litonin, D., Anikin, M., Mustaev, A., Temiakov, D. TFB2 is a transient component of the catalytic site of the human mitochondrial RNA polymerase. Cell 139, 934-944 (2009).ﾠ[http://www.ncbi.nlm.nih.gov/pubmed/19945377 Pubmed]


The spinning protein (<scene name='User:Lynmarie_K_Thompson/Sandbox_1/Loadedfrompdb/4'>Initial view</scene>) ) is the ligand binding domain of the aspartate receptor with the aspartate ligand bound (LKT).
== HELP! ==


I was unable to create Jmol scenes to illustrate structures of the human mitochondrial RNA polymerase due to a "java.security.AccessControlException: access denied" problem regardless of the computer or web browser I use.


Molecular Playground banner: A receptor protein used by bacteria to "smell" their environment.
If there is anyone that may know a remedy for this problem, please contact kmathavan@mcb.umass.edu. Thank you!
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