Who we are

Our group, consisting of biophysicists and biochemists, studies the structure and function of macromolecular assemblies using electron cryomicroscopy (cryo-EM), image analysis, biochemistry and molecular genetics. We also develop the tools of cryo-EM so that we can answer questions that are not amenable to the techniques that currently exist.

RECENT NEWS

December 01, 2019

Our home made grid preparation device publshed in Acta Cryst D

We used 3D printing, CNC milling, custom printed circuit board design, a Raspberry Pi computer, and a $3 ultrasonic humidifier to make a new type of cryoEM grid preparation device. The device can freeze a grid in ~90 msec, which allows for time resolved experiments and may prevent interactions with the air-water interface that can damage fragile protein complexes.

March 25, 2019

Thamiya's structure of the Golgi/endosomal V-ATPase published in PNAS

Yeast possess two forms of the V-ATPase: one containing the subunit a isoform Vph1p, found in the vacuole, and another containing the subunit a isoform Stv1p, found in the Golgi and endosomes. Thamiya isolated the scarce Golgi form of the enzyme and performed careful comparison with the Vacuolar form. She also determined high resolution structures of the Stv1-Vo and Vph1-Vo complexes, observing new lipid binding sites and suggesting why the Stv1-V1Vo is a slower proton pump than Vph1-V1Vo.

February 06, 2019

First structure of bacterial ATP synthase published in eLife

The bacterial ATP synthase has served as a model for understanding this important enzyme and is a drug target for antibiotics such as bedaquiline, which is used to treat multi-drug resistant and extensively drug resistant tuberculosis. Until now, no high-resolution 3D model of the structure has been available. Hui Guo has changed this situation by determining the high-resolution structure of the enzyme from Bacillus PS3.

December 09, 2019

Mycobacterial respiratory supercomplex structure published in Nature Structural and Molecular Biology

Mycobacteria, such as Mycobacterium tuberculosis, are important human pathogens. Differences between the human and mycobacterial electron transport chain can be targeted in anti-mycobacterial therapies, as shown with the drug bedaquiline that inhibits the mycobacterial ATP synthase to treat multidrug resistant and extensively drug resistant TB. In our first collaborative publication with Peter Brzezinski and co-workers in Stockholm, we determined the cryoEM structure of the CIII2CIV2 respiratory supercomplex from Mycobacterium smegmatis. We show the presence of a superoxide dismutase subunit and how the cyt. cc domain acts as an electrical switch connecting complexes III and IV.

November 01, 2018

Hui's review on ATP synthase structure published in Current Opinion in Structural Biology

A long time coming, but the review is finally published (with a major update to cover all the happened in the ATP synthase field since we submitted the first version).

October 01, 2018

Justin Di Trani joins the lab

We are delighted to welcome Dr. Justin Di Trani to the group, fresh out of his PhD at McGill. Justin's strength in physical biochemistry will be a huge asset to the group as we start to think quantitatively about analysis of protein dynamics by cryoEM.

July 10, 2018

Zev's and Siavash's manuscript on ClpP published in PNAS

Siavash and Zev show by NMR and cryoEM that ClpP is delicately balanced on the edge of a massive conformational change from its canonical barrel shape to a previously unknown split-ring structure. The change can be induced by a single point mutation in an apparently unstructured N-terminal tail of the protein. It can be reversed by binding of a small molecule activator.

May 30, 2018

May is scholarship/fellowship month!

Lots of scholarship and fellowship success in the lab:

Yazan wins CIHR Postdoctoral Fellowship

Zev wins CIHR Doctoral Scholarship

Hui wins International Student Ontario Graduate Scholarship

Congratulations to all!

April 25, 2018

Samir's and Charles' paper on the ACIII-cyt aa3 supercomplex structure published in Nature

This manuscript shows that, like Complex III and Complex IV, Alternative Complex III and Complex IV (cyt aa3) form a supercomplex, with Complex IV adapted to allow the interaction. The structure is also the first high-resolution cryo-EM structure of a membrane protein in styrene maleic acid copolymer lipid nanodisc.

March 01, 2018

Our group's work featured in the PDB's Molecule of the Month

The PDB's March 2018 Molecule of the Month is the vacuolar ATPase. David Goodsell's beautiful artwork features structures determined in our lab by Jianhua Zhao, Anna Zhou, and Dan Schep.

February 25, 2018

Yazan's review on Band 3 published in Current Opinion in Hematology

Yazan initiates our collaboration with Reinhart Reithmeier on Band 3 from the red blood cell with a review in Current Opinion in Hematology

October 26, 2017

Hui's paper on the structure of the dimeric Fo region of ATP synthase published in Science

23 years after the Nobel Prize winning structure of the F1-ATPase, Hui has revealed the structure of the Fo region of ATP synthase.

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© 2018 by John Rubinstein

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Mycobacterial respiratory complex

Key redox centers and proton pathway residues in the mycobacterial CIII(2)CIV(2) supercomplex