Our structures

Our methods aim to open up new experimental possibilities in structural biology studies. By ourselves or through collaborations, we have used our methods to determine new structures. Some of these structures are described here. For an exhaustive list, please refer to the publications list.

Tau filaments

Fitzpatrick et al (2017) Nature

In close collaboration with Michel Goedert, we determined atomic structures of the paired helical and straight filaments of the tau protein that were purified from the brain of a single individual with Alzheimer's disease. These structures reveal that residues 306-378 form the structured core of the filaments, and explain why in Alzheimer's disease a mixture of isoforms, containing both three and microtubule binding repeat regions, are incorporated into the filaments.

MacABTolC efflux pump

Fitzpatrick et al (2017) Nat. Microbiol

In close collaboration with Ben Luisi, we determined the structure of the bacterial ABC-type tripartite multidrug efflux pump formed by MacA, MacB and TolC. The structure reveals how the hexameric MacA bridges between a trimeric TolC and a dimeric MacB. The structure also identifies a gating ring in MacA, and suggests a substrate entry site from the periplasm in MacB.


E.coli replisome

Fernandez-Leiro et al (2015) eLife; Fernandez-Leiro et al (2017)Nat. Struct. Mol. Biol.

In close collaboration with Meindert Lamers, we determined a structure of the E.coli replisome comprising DNA polymerase III, clamp, exo-nuclease and tau, both with and without DNA bound. The structures reveal how a conformational change in the polymerase tail and tau may act as a molecular switch to change between processive DNA synthesis on the leading strand and discontinuous synthesis on the lagging strand.


Yeast U4/U6.U5 tri-snRNP spliceosome

Nguyen et al (2015) Nature; Nguyen et al (2016) Nature

We assisted Kiyoshi Nagai in the determination of the structure of the tri-snRNP U4/U6.U5 spliceosomal complex from yeast to a resolution of 5.9 A. The resulting pseudo-atomic model reveals the essentially complete organization of its RNA and protein components, and provides crucial insights into the activation process and the active site of the spliceosome.


Human gamma-secretase

Lu et al. (2014) Nature; Bai et al. (2015) Nature; Bai et al. (2015) eLife

We determined the structure of human gamma-secretase in collaboration with Yigong Shi from Tsinghua University. With an ordered mass of only 130 kDa, this membrane complex was thought to lie beyond the scope of current cryo-EM techniques. However, careful imaging and (novel) statistical image processing by Xiaochen Bai resulted in a 3.4 Angstrom map, which revealed the structural organization of this complex.


Drosophila and human apoptosomes

Pang et al (2015) Genes Dev.; Zhou et al (2015) Genes Dev.; Li et al. (2017) PNAS

We hosted Mengying Zhou, from Yigong Shi's lab at Tsinghua University for five months in our group to train her in cryo-EM structure determination. While she was with us, she solved several human apoptosome structures. Previously, Xiao-chen Bai in our lab had also solved a Drosophila structure as part of the same collaboration.


Rabbit ryanodine receptor

Yan et al (2015) Nature

We determined the structure of the rabbit RyR1 ryanodine receptor to 3.8 Angstrom resolution, as part of a collaboration with Nieng Yan and Yigong Shi from Tsinghua University, Beijing. The near-complete atomic model explains the high ion conductance by ryanodine receptors and the long-range allosteric regulation of their channel activities.


P. falciparum ribosome bound to emetine and mefloquine

Wong et al. (2014) eLife; Wong et al. (2017) Nat. Microbiol.

We hosted Wilson Wong, from Jake Baum's lab in Melbourne, Australia for five months in our group to determine the structure of the cytoplasmic ribosome of the malaria parasite: Plasmodium falciparum. By visualising this ribosome bound to emetine and to mefloquine, we learnt how these drugs work. These papers are an illustration of the potential of modern cryo-EM for structure-based drug design.


Mammalian ribosome:Sec61 complex

Voorhees et al (2014) Cell

We assisted Manu Hegde in the determination of the structures of the mammalian ribosome-Sec61 complex in both idle and translating states to 3.4 and 3.9 Angstrom resolution, which permitted building of a near-complete atomic model of the mammalian ribosome, visualization of A/P and P/E hybrid-state tRNAs, and analysis of a nascent polypeptide in the exit tunnel.


Mitochondrial ribosomes

Amunts et al (2014) Science; Brown et al (2014) Science; Amunts et al. (2015) Science

We assisted Venki Ramakrishnan in the determination of structures of both yeast and human mitochondrial ribosomes to near-atomic resolution. A true tour-de-force of de novo model building in the cryo-EM maps, aided by developments by Garib Murshudov and Paul Elmsley, revealed the unique architecture of ribosomal proteins and RNA in mitochondrial ribosomes compared to their cytosolic counterparts


Yeast ribosome:eIF5B complex

Fernandez et al. (2013) Science

In collaboration with Venki Ramakrishnan, we determined the structure of a eukaryotic translation initiation complex. We used cryo-EM to efficiently guide our biochemical sample preparation, and finally isolated a subset of ~3% of the particles by image classification in RELION. The corresponding 5,000 particles still give a 6.5 Angstrom map.


3D DNA-origami object

Bai et al. (2012) Proc. Natl. Acad. Sci. U S A

In collaboration with Hendrik Dietz (Technical University Munich), we determined the structure of a 3D DNA-origami object that we designed to be particularly suitable for single-particle analysis. The structure is the first of its kind and shows that DNA-origami objects are more ordered than previously thought. In addition, the structure describes a range of non-natural DNA topologies to be mined for future use in nano-technology.



Featured highlights

Human gamma-secretase

Bai et al. (2015) Nature

In collaboration with Yigong Shi from Tsinghua University in Beijing, we determined the structure of human gamma-secretase. With an ordered mass of only 130 kDa, this membrane complex was thought to lie beyond the scope of current cryo-EM techniques. However, an excellent sample from Peilong Lu, and careful imaging and statistical image processing by Xiaochen Bai resulted in a 3.4 Angstrom map, which revealed the structural organization of this exciting complex.

Near-atomic ribosome maps

Bai et al. (2013) eLife, 2:e00461

A combination of direct-electron detection and statistical movie processing to compensate for beam-induced movement allows ribosome structures to be determined from cryo-EM data to resolutions that were previously only attainable by X-ray crystallography.