Biophysics and Biophysical Chemistry

Faculty

Jon Lorsch Associate 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:	Lisa Vogt
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 26 non-ribosomal polypeptides and energy input from the hydrolysis of both ATP and GTP. We are trying to understand the molecular mechanics of this extraordinarily complex process. To do this, we are using techniques from biophysics and mechanistic enzymology and collaborate closely with yeast geneticists studying the same problems. Current projects include: 1. Kinetic and thermodynamic analysis of the steps in translation initiation in a reconstituted yeast translation system using a wide variety of biophysical techniques (e.g., fluorescence spectroscopy); 2. Enzymology of isolated initiation factors; 3. Investigations of the mechanistic roles of structural elements in the mRNA and initiator tRNA such as the 5'-7-methylguanosine cap, 3'-poly(A) tail and the consensus sequence around the initiation codon in the mRNA, and conserved bases and modifications in the initiator tRNA. We hope that dissection of the initiation process into individual steps and measurement of the physical parameters that govern each of these steps will lead towards an understanding of the molecular interactions and events responsible for the assembly of the eukaryotic translational machinery.

Relevant Publications:

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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Biophysics and Biophysical Chemistry

Johns Hopkins University School of Medicine

Departmental Office

725 N. Wolfe Street, WBSB 713

Baltimore, MD 21205-2185

410.955.8712 / FAX 410.502.6910

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