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[[Image:Screen capture of 70S white background spacefill tRNAS.jpg|left|300px]]<br />



'''The Ribosome'''<br>
'''The protein synthesis machine of cells''' <br>
'''shown with the 3 transfer RNAs and messenger RNA bound.'''





==Background==
Venkatraman Ramakrishnan of the M.R.C. Laboratory of Molecular Biology in Cambridge, England; Thomas A. Steitz of Yale University; and Ada E. Yonath of the Weizmann Institute of Science in Rehovot, Israel are being awarded the [http://nobelprize.org/nobel_prizes/chemistry/laureates/2009/ the 2009 Nobel Prize in Chemistry] for their for their landmark work revealing the atomic details of the molecular machine that make proteins in all cells, [http://en.wikipedia.org/wiki/ribosome the ribosome]. This work was the gloriously enlightening culmination of years of work, first heralded by Ada Yonath's report of crystals in 1980. Others made significant contributions to the detailed structure of this machine, as poignantly summarized by [https://loop.nigms.nih.gov/index.php/2009/10/07/2009-chemistry-nobel-prize-recognizes-the-determination-of-the-ribosomes-three-dimensional-structure/ Jeremy Berg, current Director of National Institute of General Medical Sciences, in his announcement], "The Nobel committee has the daunting challenge of limiting itself to up to three laureates for each prize. Several other long-time NIGMS grantees who also contributed greatly to our understanding of the structure and function of the ribosome include Peter Moore, Harry Noller and Joachim Frank." The American Society for Biochemistry and Molecular Biology posted [http://www.asbmb.org/News.aspx?id=3612 an announcement of the prize echoing this sentiment] as well.<br>

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 immense size of the ribosome and each of the two individual ribosomal subunits that come together to form the complete ribosome that is active in translation made for a daunting task in structure determination. These structures were at the time, and remain, the largest asymmetric molecules solved crystallographically. In addition to providing us immense insight into the general molecular and atomic details of protein synthesis in every organism on earth, the development of new antibiotics are likely to rely on this ground-breaking work.<br>

The small subunit of the ribosome is the main site of decoding, directing the interaction of the messenger RNA codon with the anticodon stem-loops of the proper transfer RNA. The formation of peptide bounds occurs in the large subunit where the acceptor-stems of the tRNAs are docked. However, it is important to keep in mind that in the active ribosome the two subunits are in contact via bridges and the actions in one subunit affect the other as the process of translation advances through the stages of initiation, elongation, and termination. The initial determination of the atomic resolution structures of the subunits surprisingly revealed that RNA and not protein contribute directly to forming the site of both decoding and catalysis of peptide bond synthesis, with the ribosomal proteins only acting in an ancillary role. During the elongation stage of translation, new peptides are added to the growing nascent chain that is linked to the acceptor-end of the tRNA in the peptidyl or P site, and as the nascent grows it advances into a tunnel that passes through the large subunit, called the polypeptide exit tunnel. Several factors can interact at the site of extrusion of the nascent polypeptide chain to insure proper folding or transport across a membrane.  Additionally, during protein synthesis, many additional factors such as EF-Tu and EF-G interact with the ribosome to elicit decoding and peptide bond synthesis accurately and efficiently. Structures of several of these factors in complex with the ribosome, as well has intermediate states in the process, are being observed now, building upon the first atomic structures.

==First Atomic-Resolution Ribosome Structures==
<b>The particular structures for which the Nobel prize was awarded were published in 2000 and were subsequently refined or improved upon. Here are the links to the Proteopedia entries</b>:

*<b>Yonath lab original atomic-resolution structures</b>: <em>Thermus thermophilus</em> small ribosomal subunit - [[1fka]], improved in [[1i94]], [[1i95]], [[1i96]], and [[1i97]]. <em>Thermus thermophilus</em> is a thermophilic eubacteria.<br>

*<b>Ramakrishnan lab original atomic-resolution structures</b>: <em>Thermus thermophilus</em> small ribosomal subunit -[[1fjf]] which was later refined to [[1j5e]]. Related: in complex with the antibiotics streptomycin, spectinomycin, and paromomycin in [[1fjg]]; in complex with tetracycline in [[1hnw]], pactamycin in [[1hnx]], hygromycin B in [[1hnz]].

*<b>Steitz and Moore lab original atomic-resolution structures</b>: <em>Haloarcula marismortui</em> large ribosomal subunit - [[1ffk]] and later refined to give [[1jj2]], and then refined to give [[1s72]]. Related: [[1ffz]], [[1fg0]]. <em>Haloracula</em> is a halophilic archaea.

==Additional Ribosome Structures==
<table width='550' align='right' cellpadding='5'><tr><td rowspan='2'>&nbsp;</td><td bgcolor='#eeeeee'><applet load='1jgo1giy.gz.pdb' size='540' frame='true' align='right' scene='User:Wayne_Decatur/SandboxRibosome/Bothmodels6/1' /></td></tr><tr><td bgcolor='#eeeeee'><center>'''The Ribosome''' (1jgo and 1giy), resolution 5.5&Aring; (<scene name='User:Wayne_Decatur/SandboxRibosome/Bothmodels6/1'>initial scene</scene>). <br>
·· {{Link Toggle 70SribotRNAs}} ·· {{Link Toggle 70SribomRNA}} ·· {{Link Toggle 70SriborRNA}} ·· {{Link Toggle 70SriboProtein}} ··<br>
·· {{Link Toggle 70SriboAsitetRNA}} ·· {{Link Toggle 70SriboPsitetRNA}} ·· {{Link Toggle 70SriboEsitetRNA}} ·· <br>
·· {{Link Toggle 70SriboLSU}} ·· {{Link Toggle 70SriboSSU}} ·· {{Link Toggle BlackWhiteBackground}}  ·· <br></center></td></tr></table>
<b>Several other ribosome structures have now been published, and here are just a few of these entries in Proteopedia (with apologies to the authors of those not yet listed):<br></b>
*[[2j00]] and [[2j01]] are the subunits of the 70S ribosome structure from the Ramakrishnan lab; the aminoglycoside antibiotic paromomycin is present as well.<br>
*[[1gix]] and [[1giy]] are the subunits of the 70S ribosome structure determined by the Noller lab, the first for the 70S at near-atomic resolution; more of the mRNA chain is seen in [[1jgo]].<br>
*[[2i2u]] and [[2i2v]] are the subunits of the <em>E. coli</em> ribosome at 3.2 &Aring; as solved by the Cate lab. [[2i2t]] and [[2i2p]] are related structures.<br>
*[[2gya]] and [[2gy9]] are the subunits of a complete <em>E. coli</em> ribosome as determined by cryo-EM by Joachim Frank's lab.<br>
*[[1ibk]] is paromomycin bound to the small subunit.<br>
*[[1ibm]] is the small subunit with an mRNA analog bound and an anticodon stem loop bound to the A site.<br>
*Small subunit bound to near-cognate tRNA anticodon stem-loop: [[1n32]], [[1n33]], [[1n34]], [[1n36]]
*Macrolide, lincosamide, streptogramin B, and ketolide antibiotics bound to the large subunit, which impacts mechanisms of drug resistance:[[1yi2]], [[1yj2]], [[1yit]], [[1yhq]], [[1yjn]], [[1yij]], [[1yj9]] <br>
*<em>E. coli</em> 70S ribosome in complex with the atypical aminoglycoside antibiotic hygromycin B: [[3df1]], [[3df2]],[[3df3]], and [[3df4]].<br>
*Ribosome Recycling Factor bound to the 70S Ribosome: [[2v46]], [[2v47]], [[2v48]], [[2v49]] <br>
*[[2ow8]] and [[1vsa]] are the subunits of a 70S-tRNA-mRNA complex from the Noller lab.<br>
*[[2e5l]] shows the small subunit with an mRNA mimic bound and the Shine-Dalgarno and anit-Shine-Dalgarno sequences interacting.<br>
*Structures of the 30S bound with anticodon stem-loops from tRNAs that facilitate frame-shifting: [[2uxb]], [[2uxc]], and [[2uxd]]
*Initation factor 1 bound to the small subunit: [[1hr0]]<br>
*70S Ribosome in complex with mRNA, paromomycin, acylated A- And P-Site tRNAs, and E-Site tRNA: [[2wdg]], [[2wdh]], [[2wdi]], [[2wdj]], [[2wdk]], [[2wdl]], [[2wdm]], and [[2wdn]]<br>
*<em>E. coli</em> 70S ribosome intermediates in a key conformational change: [[3i1m]],  [[3i1n]], [[3i1o]], [[3i1p]], [[3i1q]], [[3i1r]],[[3i1s]],[[3i1t]],[[3i1z]], [[3i20]], [[3i21]], and [[3i22]].<br>
*<em>E. coli</em> ribosome in complex with the atypical aminoglycoside antibiotic hygromycin B: [[3df1]], [[3df2]],[[3df3]], and [[3df4]].<br>
*Structural basis of a mechanism of hydrolytic release of the newly formed polypeptide by the large subunit that may be analogous to that used by release factors:[[3cma]], [[3cme]]
*Elongation factor P bound to the 70S ribosome: [[3huw]], [[3hux]], [[3huy]], [[3huz]].<br>
==The ribosome introduction scenes==
<scene name='User:Wayne_Decatur/SandboxRibosome/Bothmodels6/1'>The 70S ribosome</scene><br>
Three tRNAs and an mRNA are bound. 

<scene name='scene name='User:Wayne_Decatur/SandboxRibosome/Hidelargesubunit/3'>The small subunit, tRNAs, and mRNA</scene><br>
The anticodon stem-loops of <font color="pink">A-site tRNA</font>, <font color="purple">P-site tRNA</font>, and <font color="cyan">E-site tRNA</font> stick into the 30S subunit of the ribosome.

<scene name='User:Wayne_Decatur/SandboxRibosome/Anticodoncodonpairing/8'>Anticodon and codon pairing</scene><br>
The anticodon stem-loops of the <font color="pink">A-site tRNA</font> and <font color="purple">P-site tRNA</font> hydrogen bond to the <font color="yellow">messenger</font> RNA.

<scene name='User:Wayne_Decatur/SandboxRibosome/Largesubunitandrest/1'>The large subunit, tRNAs, and mRNA</scene>
<br>

<!--
'color firebrick' seems to be same as 'color [Xa52a2a]'
1jgo1giy.gz.pdb is the file being used.
--!>
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