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.
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.
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.