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Martin Schmeing

Martin Schmeing

Assistant Professor
Department of Biochemistry

Structure of Macromolecular Machines using X-ray crystallography and Electron Microscopy; NRPS, Ribosome

Francesco Bellini Life Sciences Building
3649 Promenade Sir William Osler
Office: Room 465; Lab: Room 456
Montreal, QC H3G 0B1
Tel: 514-398-2331; Lab: 514-398-3278
martin [dot] schmeing [at] mcgill [dot] ca
Schmeing Lab Web Page

2009 – Postdoc, LMB Cambridge
2004 – PhD, Yale University

In the news:

Le Groupe de recherche axé sur la structure des protéines (Recherche en Santé, Nov. 2012)
An Atomic View of the Ribosome (Hum-molgen news, Oct. 16, 2009)
How the genetic code is accurately translated into protein (ESRF Spotlight, Nov 10, 2009)

Research Interests

The Schmeing lab is interested in large macromolecular machines that perform important cellular processes. These enzymes often require supramolecular organization and complex architecture to function. For example, both the ribosome and some non-ribosomal peptide synthetases use more than 100,000 atoms to make peptide bonds, while the proteases that break these bonds can be very small. Of course, these assemblies require regulation, processivity and fidelity, which contribute to their increased size. Our lab investigates both the manner by which cellular machines achieve these roles, and the mechanisms of their principal functions. To do this, we combine X-ray crystallography, electron microscopy and biochemical techniques.

A. Structural Studies of Non-Ribosomal Peptide Synthetases
Non-ribosomal peptide synthetases (NRPS) are large macromolecular machines that also catalyze peptide bond formation. Instead of making proteins, these enzymes produce a large variety of small molecules with important and diverse biological activity. For example, NRPSs synthesize anti-fungals, anti-bacterials, anti-virals, anti-tumourigenics, siderophores, and immunosuppressants including well-known compounds such as penicillin and cyclosporin. NRPSs use assembly line logic, with dedicated active sites for each amino acid added to the peptide. Single subunit NRPSs can be over 2 megadaltons, and are nature’s largest known enzymes.

B. Structural Studies of the Ribosome
The ribosome is the cell’s protein factory. It translates the genetic information in mRNA into protein, rapidly and with high fidelity, using aminoacyl-tRNAs as substrates. A large number of accessory protein factors are necessary for in vivo protein synthesis, and the interplay between these factors and the ribosome is extremely complex. Deregulation of protein synthesis in humans in associated with cancers, and many important antibiotics target the bacterial ribosome.

Selected Publications

Specific disulfide cross-linking to constrict the mobile carrier domain of nonribosomal peptide synthetases. Tarry MJ, Schmeing TM. Protein Eng Des Sel. 2015 Jun;28(6):163-70. doi: 10.1093/protein/gzv009. Epub 2015 Feb 23.

Characterization of cereulide synthetase, a toxin-producing macromolecular machine. Alonzo DA, Magarvey NA, Schmeing TM. PLoS One. 2015 Jun 4;10(6)

Protospacer adjacent motif (PAM)-distal sequences engage CRISPR Cas9 DNA target cleavage. Cencic R, Miura H, Malina A, Robert F, Ethier S, Schmeing TM, Dostie J, Pelletier J. PLoS One. 2014 Oct 2;9(10)

Crystal structures of the first condensation domain of CDA synthetase suggest conformational changes during the synthetic cycle of nonribosomal peptide synthetases. Bloudoff K, Rodionov D, Schmeing TM. J Mol Biol. 2013 Sep 9;425(17):3137-50.

Crystallization and preliminary crystallographic analysis of the first condensation domain of viomycin synthetase. Bloudoff K, Schmeing TM. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2013 Apr 1;69(Pt 4):412-5.

How mutations in tRNA distant from the anticodon affect the fidelity of decoding.  Schmeing TM, Voorhees RM, Kelley AC, Ramakrishnan V. Nat Struct Mol Biol. 2011 Apr;18(4):432-6.

The mechanism for activation of GTP hydrolysis on the ribosome. Voorhees RM, Schmeing TM, Kelley AC, Ramakrishnan V. Science. 2010 Nov 5;330(6005):835-8.

The crystal structure of the ribosome bound to EF-Tu and aminoacyl-tRNA. Schmeing TM, Voorhees RM, Kelley AC, Gao YG, Murphy FV 4th, Weir JR, Ramakrishnan V. Science. 2009 Oct 30;326(5953):688-94.

What recent ribosome structures have revealed about the mechanism of translation. Schmeing TM, Ramakrishnan V. Nature. 2009 Oct 29;461(7268):1234-42.

The eukaryotic translation initiation factors eIF1 and eIF1A induce an open conformation of the 40S ribosome. Passmore LA, Schmeing TM, Maag D, Applefield DJ, Acker MG, Algire MA, Lorsch JR, Ramakrishnan V. Mol Cell. 2007 Apr 13;26(1):41-50.

An induced-fit mechanism to promote peptide bond formation and exclude hydrolysis of peptidyl-tRNA. Schmeing TM, Huang KS, Strobel SA, Steitz TA. Nature. 2005 Nov 24;438(7067):520-4.

Structural insights into the roles of water and the 2' hydroxyl of the P site tRNA in the peptidyl transferase reaction. Schmeing TM, Huang KS, Kitchen DE, Strobel SA, Steitz TA. Mol Cell. 2005 Nov 11;20(3):437-48.


Publications (complete list) - Martin Schmeing