Energy barriers and driving forces in tRNA translocation through the ribosome
Using 13 intermediate-translocation-state models derived from X-ray and cryo-EM structures of Escherichia coli ribosomes to guide large-scale molecular dynamics simulations, a new study now models the path taken by tRNAs during spontaneous translocation to uncover the mechanisms that facilitate tRNA...
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creator | Bock, Lars V Blau, Christian Schröder, Gunnar F Davydov, Iakov I Fischer, Niels Stark, Holger Rodnina, Marina V Vaiana, Andrea C Grubmüller, Helmut |
description | Using 13 intermediate-translocation-state models derived from X-ray and cryo-EM structures of
Escherichia coli
ribosomes to guide large-scale molecular dynamics simulations, a new study now models the path taken by tRNAs during spontaneous translocation to uncover the mechanisms that facilitate tRNA movement through the ribosome.
During protein synthesis, tRNAs move from the ribosome's aminoacyl to peptidyl to exit sites. Here we investigate conformational motions during spontaneous translocation, using molecular dynamics simulations of 13 intermediate-translocation-state models obtained by combining
Escherichia coli
ribosome crystal structures with cryo-EM data. Resolving fast transitions between states, we find that tRNA motions govern the transition rates within the pre- and post-translocation states. Intersubunit rotations and L1-stalk motion exhibit fast intrinsic submicrosecond dynamics. The L1 stalk drives the tRNA from the peptidyl site and links intersubunit rotation to translocation. Displacement of tRNAs is controlled by 'sliding' and 'stepping' mechanisms involving conserved L16, L5 and L1 residues, thus ensuring binding to the ribosome despite large-scale tRNA movement. Our results complement structural data with a time axis, intrinsic transition rates and molecular forces, revealing correlated functional motions inaccessible by other means. |
doi_str_mv | 10.1038/nsmb.2690 |
format | Article |
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Escherichia coli
ribosomes to guide large-scale molecular dynamics simulations, a new study now models the path taken by tRNAs during spontaneous translocation to uncover the mechanisms that facilitate tRNA movement through the ribosome.
During protein synthesis, tRNAs move from the ribosome's aminoacyl to peptidyl to exit sites. Here we investigate conformational motions during spontaneous translocation, using molecular dynamics simulations of 13 intermediate-translocation-state models obtained by combining
Escherichia coli
ribosome crystal structures with cryo-EM data. Resolving fast transitions between states, we find that tRNA motions govern the transition rates within the pre- and post-translocation states. Intersubunit rotations and L1-stalk motion exhibit fast intrinsic submicrosecond dynamics. The L1 stalk drives the tRNA from the peptidyl site and links intersubunit rotation to translocation. Displacement of tRNAs is controlled by 'sliding' and 'stepping' mechanisms involving conserved L16, L5 and L1 residues, thus ensuring binding to the ribosome despite large-scale tRNA movement. Our results complement structural data with a time axis, intrinsic transition rates and molecular forces, revealing correlated functional motions inaccessible by other means.</description><identifier>ISSN: 1545-9993</identifier><identifier>EISSN: 1545-9985</identifier><identifier>DOI: 10.1038/nsmb.2690</identifier><identifier>PMID: 24186064</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>631/337/574/1789 ; 631/535/1258/1259 ; 631/535/1267 ; 631/57/2272 ; Biochemistry ; Biological Microscopy ; Biological Transport ; Cryoelectron Microscopy ; Crystal structure ; Crystallography, X-Ray ; E coli ; Escherichia coli - genetics ; Identification and classification ; Kinetics ; Life Sciences ; Membrane Biology ; Nucleic Acid Conformation ; Protein Biosynthesis ; Protein Structure ; Protein synthesis ; Ribonucleic acid ; Ribosomes - metabolism ; Ribosomes - physiology ; RNA ; RNA, Transfer - chemistry ; RNA, Transfer - metabolism ; RNA, Transfer - physiology ; Transfer RNA ; Translocation ; Translocation (Genetics)</subject><ispartof>Nature structural & molecular biology, 2013-12, Vol.20 (12), p.1390-1396</ispartof><rights>Springer Nature America, Inc. 2013</rights><rights>COPYRIGHT 2013 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Dec 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c484t-9f6dda035c556204dafda0644172b18a1ad3fd70135272a396b8583aa20b304b3</citedby><cites>FETCH-LOGICAL-c484t-9f6dda035c556204dafda0644172b18a1ad3fd70135272a396b8583aa20b304b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24186064$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bock, Lars V</creatorcontrib><creatorcontrib>Blau, Christian</creatorcontrib><creatorcontrib>Schröder, Gunnar F</creatorcontrib><creatorcontrib>Davydov, Iakov I</creatorcontrib><creatorcontrib>Fischer, Niels</creatorcontrib><creatorcontrib>Stark, Holger</creatorcontrib><creatorcontrib>Rodnina, Marina V</creatorcontrib><creatorcontrib>Vaiana, Andrea C</creatorcontrib><creatorcontrib>Grubmüller, Helmut</creatorcontrib><title>Energy barriers and driving forces in tRNA translocation through the ribosome</title><title>Nature structural & molecular biology</title><addtitle>Nat Struct Mol Biol</addtitle><addtitle>Nat Struct Mol Biol</addtitle><description>Using 13 intermediate-translocation-state models derived from X-ray and cryo-EM structures of
Escherichia coli
ribosomes to guide large-scale molecular dynamics simulations, a new study now models the path taken by tRNAs during spontaneous translocation to uncover the mechanisms that facilitate tRNA movement through the ribosome.
During protein synthesis, tRNAs move from the ribosome's aminoacyl to peptidyl to exit sites. Here we investigate conformational motions during spontaneous translocation, using molecular dynamics simulations of 13 intermediate-translocation-state models obtained by combining
Escherichia coli
ribosome crystal structures with cryo-EM data. Resolving fast transitions between states, we find that tRNA motions govern the transition rates within the pre- and post-translocation states. Intersubunit rotations and L1-stalk motion exhibit fast intrinsic submicrosecond dynamics. The L1 stalk drives the tRNA from the peptidyl site and links intersubunit rotation to translocation. Displacement of tRNAs is controlled by 'sliding' and 'stepping' mechanisms involving conserved L16, L5 and L1 residues, thus ensuring binding to the ribosome despite large-scale tRNA movement. Our results complement structural data with a time axis, intrinsic transition rates and molecular forces, revealing correlated functional motions inaccessible by other means.</description><subject>631/337/574/1789</subject><subject>631/535/1258/1259</subject><subject>631/535/1267</subject><subject>631/57/2272</subject><subject>Biochemistry</subject><subject>Biological Microscopy</subject><subject>Biological Transport</subject><subject>Cryoelectron Microscopy</subject><subject>Crystal structure</subject><subject>Crystallography, X-Ray</subject><subject>E coli</subject><subject>Escherichia coli - genetics</subject><subject>Identification and classification</subject><subject>Kinetics</subject><subject>Life Sciences</subject><subject>Membrane Biology</subject><subject>Nucleic Acid Conformation</subject><subject>Protein Biosynthesis</subject><subject>Protein Structure</subject><subject>Protein synthesis</subject><subject>Ribonucleic acid</subject><subject>Ribosomes - metabolism</subject><subject>Ribosomes - 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Academic</collection><jtitle>Nature structural & molecular biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bock, Lars V</au><au>Blau, Christian</au><au>Schröder, Gunnar F</au><au>Davydov, Iakov I</au><au>Fischer, Niels</au><au>Stark, Holger</au><au>Rodnina, Marina V</au><au>Vaiana, Andrea C</au><au>Grubmüller, Helmut</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Energy barriers and driving forces in tRNA translocation through the ribosome</atitle><jtitle>Nature structural & molecular biology</jtitle><stitle>Nat Struct Mol Biol</stitle><addtitle>Nat Struct Mol Biol</addtitle><date>2013-12-01</date><risdate>2013</risdate><volume>20</volume><issue>12</issue><spage>1390</spage><epage>1396</epage><pages>1390-1396</pages><issn>1545-9993</issn><eissn>1545-9985</eissn><abstract>Using 13 intermediate-translocation-state models derived from X-ray and cryo-EM structures of
Escherichia coli
ribosomes to guide large-scale molecular dynamics simulations, a new study now models the path taken by tRNAs during spontaneous translocation to uncover the mechanisms that facilitate tRNA movement through the ribosome.
During protein synthesis, tRNAs move from the ribosome's aminoacyl to peptidyl to exit sites. Here we investigate conformational motions during spontaneous translocation, using molecular dynamics simulations of 13 intermediate-translocation-state models obtained by combining
Escherichia coli
ribosome crystal structures with cryo-EM data. Resolving fast transitions between states, we find that tRNA motions govern the transition rates within the pre- and post-translocation states. Intersubunit rotations and L1-stalk motion exhibit fast intrinsic submicrosecond dynamics. The L1 stalk drives the tRNA from the peptidyl site and links intersubunit rotation to translocation. Displacement of tRNAs is controlled by 'sliding' and 'stepping' mechanisms involving conserved L16, L5 and L1 residues, thus ensuring binding to the ribosome despite large-scale tRNA movement. Our results complement structural data with a time axis, intrinsic transition rates and molecular forces, revealing correlated functional motions inaccessible by other means.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>24186064</pmid><doi>10.1038/nsmb.2690</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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subjects | 631/337/574/1789 631/535/1258/1259 631/535/1267 631/57/2272 Biochemistry Biological Microscopy Biological Transport Cryoelectron Microscopy Crystal structure Crystallography, X-Ray E coli Escherichia coli - genetics Identification and classification Kinetics Life Sciences Membrane Biology Nucleic Acid Conformation Protein Biosynthesis Protein Structure Protein synthesis Ribonucleic acid Ribosomes - metabolism Ribosomes - physiology RNA RNA, Transfer - chemistry RNA, Transfer - metabolism RNA, Transfer - physiology Transfer RNA Translocation Translocation (Genetics) |
title | Energy barriers and driving forces in tRNA translocation through the ribosome |
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