Research Topics
| J R LorschSummaryAffiliation: Johns Hopkins University Country: USA Publications
Research Grants
| Collaborators
|
Detail Information
Publications
Kinetic dissection of fundamental processes of eukaryotic translation initiation in vitroJ R Lorsch
Department of Biochemistry, Beckman Center B400, Stanford University, Stanford, CA 94305 5307, USA
EMBO J 18:6705-17. 1999....- Molecular view of 43 S complex formation and start site selection in eukaryotic translation initiationJon R Lorsch
Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
J Biol Chem 285:21203-7. 2010..A molecular model is emerging in which start codon recognition is linked to dynamic reorganization of factors on the ribosome and structural changes in the ribosome itself... - Organizing graduate life sciences education around nodes and connectionsJon R Lorsch
Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Cell 146:506-9. 2011..We propose a new integrated model for graduate education in the life sciences that addresses these issues... - RNA chaperones exist and DEAD box proteins get a lifeJon R Lorsch
Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, 725 N Wolfe Street, Baltimore, MD 21205, USA
Cell 109:797-800. 2002..The RNA chaperone hypothesis suggests the existence of proteins that resolve misfolded RNA structures in vivo. A recent study has found an RNA-dependent ATPase that functions in this manner... - Yeast initiator tRNA identity elements cooperate to influence multiple steps of translation initiationLee D Kapp
Department of Biophysics and Biophysical Chemistry, Johns Hopkins University, School of Medicine, Baltimore, Maryland 21205 2185, USA
RNA 12:751-64. 2006.... - The path to perdition is paved with protonsRachel Green
Howard Hughes Medical Institute, Department of Molecular Biology and Genetics, Johns Hopkins University, 725 N Wolfe Street, Baltimore, MD 21205, USA
Cell 110:665-8. 2002..Recent studies are beginning to shed light on the mechanism of ribosome-catalyzed peptide bond formation... - Communication between eukaryotic translation initiation factors 1 and 1A on the yeast small ribosomal subunitDavid Maag
Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
J Mol Biol 330:917-24. 2003..The data presented here provide a foundation on which to build a quantitative understanding of the network of interactions between these essential factors and the rest of the initiation machinery... - Development and characterization of a reconstituted yeast translation initiation systemMikkel A Algire
Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2185, USA
RNA 8:382-97. 2002.... - The molecular mechanics of eukaryotic translationLee D Kapp
Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, Maryland 21205 2185, USA
Annu Rev Biochem 73:657-704. 2004..We discuss the mechanisms conserved across the three kingdoms of life as well as the important divergences that have taken place in the pathway... - Eukaryotic initiator tRNA: finely tuned and ready for actionSarah E Kolitz
Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
FEBS Lett 584:396-404. 2010.... - Interaction between eukaryotic initiation factors 1A and 5B is required for efficient ribosomal subunit joiningMichael G Acker
Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
J Biol Chem 281:8469-75. 2006.... - Kinetic analysis of late steps of eukaryotic translation initiationMichael G Acker
Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
J Mol Biol 385:491-506. 2009..Our data, coupled with previous work, indicate that eIF1A is present on the ribosome throughout the entire initiation process and plays key roles at every stage... - Communication between eukaryotic translation initiation factors 5 and 1A within the ribosomal pre-initiation complex plays a role in start site selectionDavid Maag
Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
J Mol Biol 356:724-37. 2006..These data suggest strongly that the interaction between eIF1A and eIF5 is involved in maintaining the fidelity of start codon recognition in vivo... - Pi release from eIF2, not GTP hydrolysis, is the step controlled by start-site selection during eukaryotic translation initiationMikkel A Algire
Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Mol Cell 20:251-62. 2005..Release of P(i), which makes GTP hydrolysis irreversible, appears to be controlled by the AUG-dependent dissociation of eIF1 from the preinitiation complex... - Kinetic and thermodynamic analysis of the role of start codon/anticodon base pairing during eukaryotic translation initiationSarah E Kolitz
Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
RNA 15:138-52. 2009..This induced-fit mechanism supports the proposal that initiation codon recognition by the 43S complex induces a conformational change from an open state to a closed one that arrests movement along the mRNA... - A conformational change in the eukaryotic translation preinitiation complex and release of eIF1 signal recognition of the start codonDavid Maag
Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Mol Cell 17:265-75. 2005..These rearrangements probably play a role in triggering GTP hydrolysis and committing the complex to downstream events... - The 5'-7-methylguanosine cap on eukaryotic mRNAs serves both to stimulate canonical translation initiation and to block an alternative pathwaySarah F Mitchell
Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Mol Cell 39:950-62. 2010.... - Should I stay or should I go? Eukaryotic translation initiation factors 1 and 1A control start codon recognitionSarah F Mitchell
Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
J Biol Chem 283:27345-9. 2008..Both factors perform their tasks through a variety of interactions with other components of the initiation machinery, in many cases mediated by the unstructured regions of the two proteins... - Mechanism of ribosomal subunit joining during eukaryotic translation initiationMichael G Acker
Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Biochem Soc Trans 36:653-7. 2008.... - Where to begin? The mechanism of translation initiation codon selection in eukaryotesMikkel A Algire
Johns Hopkins University School of Medicine, Department of Biophysics and Biophysical Chemistry, Baltimore, MD 21205, USA
Curr Opin Chem Biol 10:480-6. 2006.... - GTP-dependent recognition of the methionine moiety on initiator tRNA by translation factor eIF2Lee D Kapp
Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, 725 N. Wolfe Street 625 WBSB, Baltimore, MD 21205-2185, USA
J Mol Biol 335:923-36. 2004..Our data suggest that a role of this base-pair is to orient the methionine moiety on the initiator tRNA in its recognition pocket on eIF2... - Reconstitution of yeast translation initiationMichael G Acker
Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Methods Enzymol 430:111-45. 2007..1998; Trachsel et al., 1977). The following describes methods for synthesizing and purifying the components of the yeast initiation system and assays useful for its characterization... - eIF1 controls multiple steps in start codon recognition during eukaryotic translation initiationJagpreet S Nanda
Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
J Mol Biol 394:268-85. 2009..Our data indicate that eIF1 plays multiple roles in start codon recognition and suggest that prior to AUG recognition it prevents eIF5 from binding to a key site in the PIC required for triggering downstream events... - N- and C-terminal residues of eIF1A have opposing effects on the fidelity of start codon selectionChristie A Fekete
Laboratory of Gene Regulation and Development, National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892, USA
EMBO J 26:1602-14. 2007..We conclude that tight binding of eIF1A to the PIC is an important determinant of AUG selection and is modulated in opposite directions by residues in the NTT and CTT of eIF1A... - Uncoupling of initiation factor eIF5B/IF2 GTPase and translational activities by mutations that lower ribosome affinityByung Sik Shin
Laboratory of Gene Regulation and Development, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
Cell 111:1015-25. 2002..The translational defect suggests eIF5B stabilizes Met-tRNA(i)(Met) binding and that GTP hydrolysis by eIF5B is a checkpoint monitoring 80S ribosome assembly in the final step of translation initiation... - Ribozyme catalysis: not different, just worseJennifer A Doudna
Department of Molecular and Cell Biology, Howard Hughes Medical Institute, University of California at Berkeley, Berkeley, California 94720, USA
Nat Struct Mol Biol 12:395-402. 2005..These findings make it increasingly possible to compare details of RNA- and protein-based catalysis... - Coupled release of eukaryotic translation initiation factors 5B and 1A from 80S ribosomes following subunit joiningJeanne M Fringer
Laboratory of Gene Regulation and Development, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
Mol Cell Biol 27:2384-97. 2007..Following 80S complex formation, GTP hydrolysis by eIF5B enables the release of both eIF5B and eIF1A, and the ribosome enters the elongation phase of protein synthesis... - Genetic identification of yeast 18S rRNA residues required for efficient recruitment of initiator tRNA(Met) and AUG selectionJinsheng Dong
Laboratory of Gene Regulation and Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892, USA
Genes Dev 22:2242-55. 2008..Hence, the nonconserved 928:1389 base pair in h28, plus conserved 18S rRNA residues corresponding to P-site contacts in bacterial ribosomes, are critical for efficient Met-tRNA(i)(Met) binding and AUG selection in eukaryotes... - Intragenic suppressor mutations restore GTPase and translation functions of a eukaryotic initiation factor 5B switch II mutantByung Sik Shin
NIH, 6 Center Dr, Bldg 6A, Rm B1A 03, Bethesda, MD 20892, USA
Mol Cell Biol 27:1677-85. 2007..Accordingly, the Switch I and domain II suppressor mutations induce Switch II to adopt a conformation favorable for nucleotide binding and hydrolysis and thereby reestablish coupling between GTP binding and eIF5B domain movements... - The eIF1A C-terminal domain promotes initiation complex assembly, scanning and AUG selection in vivoChristie A Fekete
Laboratory of Gene Regulation and Development, National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892, USA
EMBO J 24:3588-601. 2005..Thus, the OB-fold is crucial for ribosome-binding and the C-terminal domain of eIF1A has eukaryotic-specific functions in TC recruitment and scanning... - Dissociation of eIF1 from the 40S ribosomal subunit is a key step in start codon selection in vivoYuen Nei Cheung
Laboratory of Gene Regulation and Development, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA
Genes Dev 21:1217-30. 2007.... - The eukaryotic translation initiation factors eIF1 and eIF1A induce an open conformation of the 40S ribosomeLori A Passmore
MRC Laboratory of Molecular Biology, Hills Road, Cambridge, UK
Mol Cell 26:41-50. 2007..Our results suggest that eIF1 and eIF1A promote an open, scanning-competent preinitiation complex that closes upon start codon recognition and eIF1 release to stabilize ternary complex binding and clamp down on mRNA... - Initiation of protein synthesis by hepatitis C virus is refractory to reduced eIF2.GTP.Met-tRNA(i)(Met) ternary complex availabilityFrancis Robert
Department of Biochemistry and McGill Cancer Center, McGill University, Montreal, Quebec, Canada
Mol Biol Cell 17:4632-44. 2006..Analysis of initiation complexes formed on the HCV IRES in the presence of inhibitor indicates that eIF2alpha and Met-tRNA(i)(Met) are present, defining a tactic used by HCV to evade part of the antiviral interferon response...
Research Grants
- KINETIC DISSECTION OF EUKARYOTIC TRANSLATION INITIATIONJon R Lorsch; Fiscal Year: 2010..Our studies will increase our understanding of how translation normally works, which in turn will increase our understanding of how it can break down and result in diseases. ..
- KINETIC DISSECTION OF EUKARYOTIC TRANSLATION INITIATIONJon Lorsch; Fiscal Year: 2009..These studies will thus synergistically harness the power of yeast genetics and molecular biology to the detailed biophysical and biochemical studies possible in vitro. ..
- KINETIC DISSECTION OF EUKARYOTIC TRANSLATION INITIATIONJon Lorsch; Fiscal Year: 2009..These studies will thus synergistically harness the power of yeast genetics and molecular biology to the detailed biophysical and biochemical studies possible in vitro. ..
- KINETIC DISSECTION OF EUKARYOTIC TRANSLATION INITIATIONJon Lorsch; Fiscal Year: 2007..These studies will thus synergistically harness the power of yeast genetics and molecular biology to the detailed biophysical and biochemical studies possible in vitro. ..
- Small Molecule Effectors of Eukaryotic Translation Initiation Site SelectionJon Lorsch; Fiscal Year: 2007..A deeper understanding of this complex cellular machine could lead to new approaches to treat the myriad diseases that affect the ribosome's function. ..
- KINETIC DISSECTION OF EUKARYOTIC TRANSLATION INITIATIONJon Lorsch; Fiscal Year: 2005..The studies outlined in this proposal will lay the foundation for many years of work aimed at understanding the molecular basis for each event required for eukaryotic translation initiation. ..
- KINETIC DISSECTION OF EUKARYOTIC TRANSLATION INITIATIONJon R Lorsch; Fiscal Year: 2010..Our studies will increase our understanding of how translation normally works, which in turn will increase our understanding of how it can break down and result in diseases. ..