Biophysics and Biophysical Chemistry

Faculty

Jon Lorsch Professor Johns Hopkins University School of Medicine 725 N. Wolfe St., 625 WBSB Baltimore, MD 21205
Phone:	410-955-3012
Fax:	410-955-0637
Lab:	410-955-3064
Email:	jlorsch@jhmi.edu
Assistant:	Catherine Kates
Web	http://biophysics.med.jhmi.edu/lorsch/

Complete List of Publications

Research Interests:

In eukaryotes, assembly of a ribosome on an mRNA (translation initiation) requires the action of at least 12 initiation factors and energy input from the hydrolysis of both ATP and GTP. Translation initiation is a key point in the control of gene expression and breakdown of proper initiation and its control play roles in a number of human diseases. Our lab uses a fully reconstituted yeast-based translation initiation system and a wide variety of biochemical and biophysical methods to dissect the molecular mechanics of this central biological process. We collaborate closely with geneticists and structural biologists in order to build a complete picture of the operation of the eukaryotic translational machinery. We are also developing chemical reagents to control translation initiation, with the hope that they may some day become drugs.

Relevant Publications:

Mitchell, S.F., S.E. Walker, M.A. Algire, E.H. Park, A.G. Hinnebusch, and J.R. Lorsch. (2010) The 5'-7-methylguanosine cap on eukaryotic mRNAs serves both to stimulate canonical translation initiation and to block an alternative pathway. Mol. Cell 39:950-962.

Saini, A.K., J.S. Nanda, J.R. Lorsch, and A.G. Hinnebusch. (2010) Regulatory elements in eIF1A control the fidelity of start codon selection by modulating tRNA(i)(Met) binding to the ribosome. Genes Dev. 24:97-110.

Nanda, J.S., Y.N. Cheung, J.E. Takacs, P. Martin-Marcos, A.K. Saini, A.G. Hinnebusch, and J.R. Lorsch. (2009) eIF1 controls multiple steps in start codon recognition during eukaryotic translation initiation. J. Mol. Biol. Sep 12. [Epub ahead of print] PMID: 19751744

Kolitz, S.E., J.E. Takacs, and J.R. Lorsch. (2009) Kinetic and thermodynamic analysis of the role of start codon/anticodon base pairing during eukaryotic translation initiation. RNA 15:138-152.

Acker, M.G., B.S. Shin, J.S. Nanda, A.K. Saini, T.E. Dever, and J.R. Lorsch. (2009) Kinetic analysis of late steps of eukaryotic translation initiation. J. Mol. Biol. 385:491-506.

Cheung, Y.N., D. Maag, S.F. Mitchell, C.A. Fekete, M.A. Algire, J.E. Takacs, N. Shirokikh, T. Pestova, J.R. Lorsch, and A.G. Hinnebusch. (2007) Dissociation of eIF1 from the 40S ribosomal subunit is a key step in start codon selection in vivo. Genes Dev. 21:1217-30.

Passmore, L.A., T.M. Schmeing, D. Maag, D.J. Applefield, M.G. Acker, M.A. Algire, J.R. Lorsch, and V. Ramakrishnan. (2007) The eukaryotic translation initiation factors eIF1 and eIF1A induce an open conformation of the 40S ribosome. Mol. Cell 26:41-50.

Fekete, C.A., S.F. Mitchell, V.A. Cherkasova, D. Applefield, M.A. Algire, D. Maag, A.K. Saini, J.R. Lorsch, and A.G. Hinnebusch. (2007) N- and C-terminal residues of eIF1A have opposing effects on the fidelity of start codon selection. EMBO J. 26:1602-14.

Kapp LD, Kolitz SE, Lorsch JR. (2006) Yeast initiator tRNA identity elements cooperate to influence multiple steps of translation initiation. RNA 12:751-64.

Acker MG, Shin BS, Dever TE, Lorsch JR. (2006) Interaction between eukaryotic initiation factors 1A and 5B is required for efficient ribosomal subunit joining. J. Biol. Chem. 281:8469-75.

Maag, D., M.A. Algire, and J.R. Lorsch. (2006) Communication between eukaryotic translation initiation factors 5 and 1A within the ribosomal pre-initiation complex plays a role in start site selection. J. Mol. Biol. 356:724-37.

Algire, M.A., D. Maag, and J.R. Lorsch. (2005) Pi release from eIF2, not GTP hydrolysis, is the step controlled by start-site selection during eukaryotic translation initiation. Mol. Cell 20:251-262.

Fekete, C.A., D.J. Applefield, S.A. Blakely, N. Shirokikh, T. Pestova, J.R. Lorsch, and A.G. Hinnebusch. (2005) The eIF1A C-terminal domain promotes initiation complex assembly, scanning and AUG selection in vivo. EMBO J. 24:3588-3601.

Doudna, J.A. and J.R. Lorsch. (2005) Ribozyme catalysis: not different, just worse. Nat. Struct. Mol. Biol. 12:395-402. Review.

Maag, D., C.A. Fekete, Z. Gryczynski and J.R. Lorsch. (2005) A conformational change in the eukaryotic translation preinitiation complex and release of elF1 signal recognition of the start codon. Mol. Cell 17:265-275.

Kapp, L.D. and J.R. Lorsch. (2004) The molecular mechanics of eukaryotic translation. Ann. Rev. Biochem. 73:657-704.

Kapp, L.D. and J.R. Lorsch. (2004) GTP-dependent recognition of the methionine moiety on initiator tRNA by translation factor elF2. J. Mol. Biol. 335:923-936.

Maag, D. and J.R. Lorsch. (2003) Communication between eukaryotic translation initiation factors 1 and 1A on the yeast small ribosomal subunit. J. Mol. Biol. 330:917-924.

Shin, B.-S., D. Maag, A. Roll-Mecak, M.S. Arefin, S.K. Burley, J.R. Lorsch and T.E. Dever. (2002) Uncoupling of initiation factor eIF5B/IF2 GTPase and Translational Activities by Mutations that Lower Ribosome Affinity. Cell 111:1015-1025.

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