User:Wayne Decatur/Haloarcula Large Ribosomal Subunit: Difference between revisions
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==Introduction== | ==Introduction== | ||
The [[ribosome]] is a complex composed of RNA and protein that adds up to several million daltons in size and plays a critical role in the process of decoding the genetic information stored in the genome into protein as outlined in what is now known as [http://sandwalk.blogspot.com/2009/10/ribosome-and-central-dogma-of-molecular.html the Central Dogma of Molecular Biology]. Specifically, the ribosome carries out the process of translation, decoding the genetic information encoded in messenger RNA, one amino acid at a time, into newly synthesized polypeptide chains. The ribosome functions as a complex of two complexes of many proteins and RNAs of substantial length; these two complexes are the small ribosomal subunit and the large ribosomal subunit. The formation of peptide bonds occurs in the large subunit where the acceptor-stems of the tRNAs are docked. | The [[ribosome]] is a complex composed of RNA and protein that adds up to several million daltons in size and plays a critical role in the process of decoding the genetic information stored in the genome into protein as outlined in what is now known as the Central Dogma of Molecular Biology<ref>[http://sandwalk.blogspot.com/2009/10/ribosome-and-central-dogma-of-molecular.html the Central Dogma of Molecular Biology clarified]</ref>. Specifically, the ribosome carries out the process of translation, decoding the genetic information encoded in messenger RNA, one amino acid at a time, into newly synthesized polypeptide chains. The ribosome functions as a complex of two complexes of many proteins and RNAs of substantial length; these two complexes are the small ribosomal subunit and the large ribosomal subunit. The formation of peptide bonds occurs in the large subunit where the acceptor-stems of the tRNAs are docked. | ||
In 2000, the large ribosomal subunit from <em>Haloracula marismortui</em> was solved. <em>Haloracula</em> is a [[Extremophiles|halophilic]] archaea. '''The structure revealed that surprisingly no protein was observed close enough the site of peptide bond synthesis to be be involved in the chemistry of the peptidyl transferase reaction, meaning that RNA was responsible for catalysis and that the large subunit is a ribozyme'''. The structure also revealed the details of the tunnel which the nascent peptide chain would exit the ribosome. | In 2000, the large ribosomal subunit from <em>Haloracula marismortui</em> was solved. <em>Haloracula</em> is a [[Extremophiles|halophilic]] archaea. '''The structure revealed that surprisingly no protein was observed close enough the site of peptide bond synthesis to be be involved in the chemistry of the peptidyl transferase reaction, meaning that RNA was responsible for catalysis and that the large subunit is a ribozyme'''. The structure also revealed the details of the tunnel which the nascent peptide chain would exit the ribosome. | ||
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==Thomas Steitz shares a 2009 Nobel Prize for The Haloarcula Large Ribosomal Subunit Structure== | ==Thomas Steitz shares a 2009 Nobel Prize for The Haloarcula Large Ribosomal Subunit Structure== | ||
For this landmark structure, Thomas A. Steitz of Yale University shared [http://nobelprize.org/nobel_prizes/chemistry/laureates/2009/ | For this landmark structure, Thomas A. Steitz of Yale University shared [[Nobel Prizes for 3D Molecular Structure#Twenty-First Century|the 2009 Nobel Prize in Chemistry]]<ref>[http://nobelprize.org/nobel_prizes/chemistry/laureates/2009/ The Nobel Prize in Chemistry 2009 page at The Official Web Site of the Nobel Prize]</ref><ref>PMID: 20509130</ref> along with two other structural biologists working on the ribosome. It is important to note that the Steitz lab worked with the Moore lab on this phenomenal accomplishment although the Nobel committee limits the award itself to up to three laureates. | ||
This structure ranks among the [[Highest impact structures|known structures with highest impact]]. | This structure ranks among the [[Highest impact structures|known structures with highest impact]]. | ||
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===The rRNA domains:=== | ===The rRNA domains:=== | ||
The secondary structure map of Haloarcula 23S rRNA (below) clearly shows six large RNA domains extending off a large major loop. | The secondary structure map of Haloarcula 23S rRNA (below) clearly shows six large RNA domains extending off a large major loop.<br> | ||
[[Image:Schematic hmarlsu.jpg|left]] | [[Image:Schematic hmarlsu.jpg|left]] | ||
<table width='400' align='right' cellpadding='5'><tr><td rowspan='2'> </td><td bgcolor='#eeeeee'><applet load='1s72ALPHACplusccapurowithCERTAINSIDECHAINS.PDB' size='540' frame='true' align='right' scene='User:Wayne_Decatur/Sandbox_Haloarcula_Ribosomal_Large_Subunit/1s72beststart/3' /></td></tr><tr><td bgcolor='#eeeeee'><center>'''The Large Ribosomal Subunit''' ([[1s72]]), resolution 2.4Å (<scene name='User:Wayne_Decatur/Sandbox_Haloarcula_Ribosomal_Large_Subunit/1s72beststart/3'>initial scene</scene>). <br> | <table width='400' align='right' cellpadding='5'><tr><td rowspan='2'> </td><td bgcolor='#eeeeee'><applet load='1s72ALPHACplusccapurowithCERTAINSIDECHAINS.PDB' size='540' frame='true' align='right' scene='User:Wayne_Decatur/Sandbox_Haloarcula_Ribosomal_Large_Subunit/1s72beststart/3' /></td></tr><tr><td bgcolor='#eeeeee'><center>'''The Large Ribosomal Subunit''' ([[1s72]]), resolution 2.4Å (<scene name='User:Wayne_Decatur/Sandbox_Haloarcula_Ribosomal_Large_Subunit/1s72beststart/3'>initial scene</scene>). <br> | ||
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:*<scene name='User:Wayne_Decatur/Sandbox_Haloarcula_Ribosomal_Large_Subunit/1s72rrnadomain3/6'>Domain III</scene> (<font color = "yellow">'''shown in yellow'''</font>) | :*<scene name='User:Wayne_Decatur/Sandbox_Haloarcula_Ribosomal_Large_Subunit/1s72rrnadomain3/6'>Domain III</scene> (<font color = "yellow">'''shown in yellow'''</font>) | ||
:*<scene name='User:Wayne_Decatur/Sandbox_Haloarcula_Ribosomal_Large_Subunit/1s72rrnadomain4/7'>Domain IV</scene> (<font color = "#00FF00">'''shown in green'''</font>) | :*<scene name='User:Wayne_Decatur/Sandbox_Haloarcula_Ribosomal_Large_Subunit/1s72rrnadomain4/7'>Domain IV</scene> (<font color = "#00FF00">'''shown in green'''</font>) | ||
::*<small>Helix 69 is a portion of Domain IV | ::*<small>Helix 69 is a portion of Domain IV <ref>Helix 69 is shown clearly in Domain IV in [http://people.biochem.umass.edu/fournierlab/3dmodmap/hmarlsu2dframes.php a detailed secondary structure of Haloarcula marismortui 23S rRNA]</ref>and is part of one of the important conserved intersubunit bridges of the ribosome (b2a), although '''it is not visible in this structure'''. (The 13-nt stem-loop not seen would connect the highlighted spheres <scene name='User:Wayne_Decatur/Sandbox_Haloarcula_Ribosomal_Large_Subunit/1s72rrnadomain4h69/2'>here</scene>.) See the [[ribosome]] to see a structure where helix 69 is observed in the solved structure, extending from the large subunit under the A- and P- site tRNAs in the 70S ribosome and contacting the tRNAs and the small subunit decoding center. Helix 69 plays a roles in initiation, termination, and disassembly of the ribosome post-termination</small><ref>PMID: 17996252</ref><ref>PMID: 19007789</ref><ref>PMID: 16973438</ref>. | ||
:*<scene name='User:Wayne_Decatur/Sandbox_Haloarcula_Ribosomal_Large_Subunit/1s72rrnadomain5/6'>Domain V</scene> (<font color = "red">'''shown in red'''</font>) | :*<scene name='User:Wayne_Decatur/Sandbox_Haloarcula_Ribosomal_Large_Subunit/1s72rrnadomain5/6'>Domain V</scene> (<font color = "red">'''shown in red'''</font>) | ||
::*<font color="red">'''Domain V'''</font> lies at the core of the subunit. It is known to be intimately associated with the peptidyl transferase reaction that occurs during translation. This is further explored further [[#The ribosome is a ribozyme - protein DOES NOT participate directly in the chemistry of peptide bond synthesis:|below]]. | ::*<font color="red">'''Domain V'''</font> lies at the core of the subunit. It is known to be intimately associated with the peptidyl transferase reaction that occurs during translation. This is further explored further [[#The ribosome is a ribozyme - protein DOES NOT participate directly in the chemistry of peptide bond synthesis:|below]]. | ||
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:*Using the mouse to spin around the structure clearly shows that the extended proteins penetrate into the interior to fill gaps between RNA secondary structure elements. | :*Using the mouse to spin around the structure clearly shows that the extended proteins penetrate into the interior to fill gaps between RNA secondary structure elements. | ||
:*The globular domains are the portions of the proteins on the subunit's exterior, nestling in the gaps and crevices of the folded RNA. You may need to use the mouse to move the structure around to convince yourself. | :*The globular domains are the portions of the proteins on the subunit's exterior, nestling in the gaps and crevices of the folded RNA. You may need to use the mouse to move the structure around to convince yourself. | ||
:*This view is also a good point to note the fact that the ribosomal proteins do not encase the nucleic acid as with [ | :*This view is also a good point to note the fact that the ribosomal proteins do not encase the nucleic acid as with [[Human Immunodeficiency Virus|spherical viruses]] or with [[1vtm|Tobacco mosaic virus]], nor do the proteins become surrounded by the nucleic acid as in the [[Nucleosomes|nucleosome]]. | ||
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:*Examining the distance of the proteins from the '''phosphorous analog of the tetrahedral carbon''' (<font color="yellow">'''in yellow'''</font>) indicates none of the proteins are close enough to be involved in the chemistry of peptide bond synthesis. '''Even the closest protein is over 15 Å away'''.<small>(In the eubacterial ribosomes , e.g., [[2j01]],[[2i2v]], and [[2wdn]], the N-terminus of a non-universally conserved protein, L27, also comes close to the active site<ref>PMID: 16285924</ref><ref>PMID: 18393533</ref><ref>PMID: 19363482</ref>.)</small> | :*Examining the distance of the proteins from the '''phosphorous analog of the tetrahedral carbon''' (<font color="yellow">'''in yellow'''</font>) indicates none of the proteins are close enough to be involved in the chemistry of peptide bond synthesis. '''Even the closest protein is over 15 Å away'''.<small>(In the eubacterial ribosomes , e.g., [[2j01]],[[2i2v]], and [[2wdn]], the N-terminus of a non-universally conserved protein, L27, also comes close to the active site<ref>PMID: 16285924</ref><ref>PMID: 18393533</ref><ref>PMID: 19363482</ref>.)</small> | ||
:*As touched on earlier in this section as well as [[#The rRNA domains:|in an earlier section]], it is in fact, <scene name='User:Wayne_Decatur/Sandbox_Haloarcula_Ribosomal_Large_Subunit/1s72ribozymewprna/2'>the RNA of Domain V that is intimately associated with the active site of the ribosome</scene>, leaving little doubt that the ribosome is indeed a ribozyme. | :*As touched on earlier in this section as well as [[#The rRNA domains:|in an earlier section]], it is in fact, <scene name='User:Wayne_Decatur/Sandbox_Haloarcula_Ribosomal_Large_Subunit/1s72ribozymewprna/2'>the RNA of Domain V that is intimately associated with the active site of the ribosome</scene>, leaving little doubt that the ribosome is indeed a ribozyme. | ||
::*<small>Keep in mind that in order to make this | ::*<small>Keep in mind that in order to make this large molecule load in reasonable times over the internet, the RNA has been simplified by leaving out the information for most of the bases and in fact if all the bases were included it would look even more crowded with RNA at the active site.</small> | ||
:'''SUMMARY: Only RNA is in proximity to the site of peptide bond synthesis, and therefore the chemistry of peptide bond synthesis is not catalyzed by protein and in fact the ribosome is a ribozyme with the peptidyl transferase reaction being catalyzed by RNA'''. | :'''SUMMARY: Only RNA is in proximity to the site of peptide bond synthesis, and therefore the chemistry of peptide bond synthesis is not catalyzed by protein and in fact the ribosome is a ribozyme with the peptidyl transferase reaction being catalyzed by RNA'''. | ||
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==Structures== | ==Structures== | ||
<b>Steitz and Moore labs original atomic-resolution structures</b><ref>PMID:10937989</ref><ref>PMID: 10937990</ref>: <em>Haloarcula marismortui</em> large ribosomal subunit - [[1ffk]] and later refined to give [[1jj2]]<ref>PMID:11483524</ref>, and then refined to give [[1s72]]<ref>PMID:15184028</ref>, and later [[3cc2]]<ref>PMID:18455733</ref>. Related: [[1ffz]], [[1fg0]]. Assembled with the ribosomal RNAs (2,922 and 122 nucleotides long) in the structure are 27 protein chains (of a total of 31 known), varying in length from 49 (L39E, 6 kDa) to 337 amino acids (L3, 37 kDa).<ref>PMID:10937989</ref> | <b>Steitz and Moore labs original atomic-resolution structures</b><ref>PMID:10937989</ref><ref>PMID: 10937990</ref>: <em>Haloarcula marismortui</em> large ribosomal subunit - [[1ffk]] and later refined to give [[1jj2]]<ref>PMID:11483524</ref>, and then refined to give [[1s72]]<ref>PMID:15184028</ref>, [[2qa4]]<ref>PMID:17599351</ref>, and later [[3cc2]]<ref>PMID:18455733</ref>. Related: [[1ffz]], [[1fg0]]. Assembled with the ribosomal RNAs (2,922 and 122 nucleotides long) in the structure are 27 protein chains (of a total of 31 known), varying in length from 49 (L39E, 6 kDa) to 337 amino acids (L3, 37 kDa).<ref>PMID:10937989</ref> | ||
Specifically used on this page were [[1s72]] with Yarus analog interacting nucleotides from [[1ffz]]. | Specifically used on this page were [[1s72]] with Yarus analog interacting nucleotides from [[1ffz]]. | ||
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* [[Extremophiles]] | * [[Extremophiles]] | ||
* [[Highest impact structures]] of all time | * [[Highest impact structures]] of all time | ||
* [[1nkw]] – The Large Ribosomal Subunit From ''Deinococcus radiodurans'' | |||
* [[User:Wayne Decatur/kink-turn motif|Kink-turn motif]] – analysis of the ''Haloarcula'' large ribosomal subunit revealed a common RNA motif. The location of the kink-turns in the ''Haloarcula'' large ribosomal subunit are shown on [[User:Wayne Decatur/kink-turn motif|this page]]. | |||
==References== | ==References and Notes== | ||
<references /> | <references /> | ||
==Additional Literature | ==Additional Literature== | ||
<ref group="xtra">PMID:19222865</ref><ref group="xtra">PMID: 18292779</ref><ref group="xtra">PMID: 19962317</ref><ref group="xtra">PMID: 19838167</ref><ref group="xtra">PMID: 11297922</ref><ref group="xtra" | <ref group="xtra">PMID:19222865</ref><ref group="xtra">PMID: 18292779</ref><ref group="xtra">PMID: 19962317</ref><ref group="xtra">PMID: 19838167</ref><ref group="xtra">PMID: 11297922</ref><ref group="xtra">PMID: 20562215</ref><ref group="xtra">PMID: 23771137</ref><references group="xtra"/> | ||
==External Resources== | |||
*[http://www.pdb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb121_1.html 70S Ribosome: January 2010 Molecule of the Month] as part of the series of tutorials that are at [http://www.pdb.org/pdb/home/home.do the RCSB Protein Data Bank] and written by [[User:David_S._Goodsell|David Goodsell]] | |||
*[http://www.rcsb.org/pdb/static.do?p=general_information/news_publications/news/news_2009.html#20091013 RCSB Protein Data Bank coverage of the 2009 Nobel Prizes in Chemistry] | *[http://www.rcsb.org/pdb/static.do?p=general_information/news_publications/news/news_2009.html#20091013 RCSB Protein Data Bank coverage of the 2009 Nobel Prizes in Chemistry] | ||
*[http:// | *[http://nobelprize.org/nobel_prizes/chemistry/laureates/2009/ The Nobel Prize in Chemistry 2009 page at The Official Web Site of the Nobel Prize] | ||
*[http://www.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb10_1.html Ribosome: October 2000 Molecule of the Month] as part of the series of tutorials that are at [http://www.pdb.org/pdb/home/home.do the RCSB Protein Data Bank] and written by [[User:David_S._Goodsell|David Goodsell]] | *[http://www.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb10_1.html Ribosome: October 2000 Molecule of the Month] as part of the series of tutorials that are at [http://www.pdb.org/pdb/home/home.do the RCSB Protein Data Bank] and written by [[User:David_S._Goodsell|David Goodsell]] | ||
* | *[http://apollo.chemistry.gatech.edu/RiboVision/ RiboVision] - a nice way to explore the representative structures with the secondary structures of the RNA side-by-side with the 3D structure, from from Georgia Institute of Technology and NASA. | ||
*The people behind [http://apollo.chemistry.gatech.edu/RiboVision/ RiboVision] have determined a [http://nar.oxfordjournals.org/content/41/15/7522.short?rss=1 revised secondary structure for two of the rRNAs] based on the 3D structures and it is described in [http://www.ncbi.nlm.nih.gov/pubmed/23771137?dopt=Abstract their paper]<ref group="xtra">PMID: 23771137</ref>. | |||
* [http://people.biochem.umass.edu/fournierlab/3dmodmap/hmarlsu2dframes.php A detailed secondary structure of Haloarcula marismortui 23S rRNA] at the [http://people.biochem.umass.edu/fournierlab/3dmodmap/main.php 3D Ribosomal Modifications Map Database] | |||
[[Category: Haloarcula marismortui]] | [[Category: Haloarcula marismortui]] | ||
[[Category: Klein, D J.]] | [[Category: Klein, D J.]] | ||
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[[Category: Schmeing, T M.]] | [[Category: Schmeing, T M.]] | ||
[[Category: Steitz, T A.]] | [[Category: Steitz, T A.]] | ||
[[Category: Ban, N.]] | |||
[[Category: Hansen, J.]] | |||
[[Category: Nissen, P.]] | |||
[[Category: Blaha, G.]] | |||
[[Category: Gurel, G.]] | |||
[[Category: Schroeder, S J.]] | |||
[[Category: Genomic sequnece for r-protein]] | |||
[[Category: Metal-binding]] | |||
[[Category: Protein-protein]] | [[Category: Protein-protein]] | ||
[[Category: Protein-rna]] | [[Category: Protein-rna]] | ||
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[[Category: A-minor motif]] | [[Category: A-minor motif]] | ||
[[Category: ribose zipper]] | [[Category: ribose zipper]] | ||
[[Category: Acetylation]] | |||
[[Category: Rna-binding]] | |||
[[Category: Rrna-binding]] | |||
[[Category: Trna-binding]] | |||
[[Category: Zinc]] | |||
[[Category: Zinc-finger]] | |||
[[Category: RNA]] | |||