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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

2004 – PhD, Yale University

In the news:
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 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.

B. 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.

Selected Publications

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

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

Schmeing TM, Voorhees RM, Kelley AC, Gao YG, Murphy FV 4th, Weir JR, & Ramakrishnan V. (2009) The Crystal Structure of the Ribosome Bound to EF-Tu and Aminoacyl-tRNA. Science 326(5953):688-693.

Schmeing TM & Ramakrishnan V (2009) What recent ribosome structures have revealed about the mechanism of translation. Nature 461(7268):1234-1242.

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

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

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

Publications (complete list) - Martin Schmeing