Dr. John Rubinstein

Atomic model for the membrane-embedded motor of a eukaryotic V-ATPase

Proton pumping region of rotary ATPases revealed

3 November 2016|

In work led by postdoctoral fellow Mohammad T. Mazhab-Jafari, the Rubinstein laboratory used electron cryomicroscopy (cryo-EM) to determine the atomic structure of the membrane-bound region of a eukaryotic V-ATPase. This study, which was published in Nature, gives the first high-resolution structure for the membrane region of any rotary ATPase, a family of enzymes that includes proton pumping V-ATPases and proton-driven ATP synthases. The structure reveals several surprising features of […]

An image of models for two conformations of the AAA+ chaperone VAT, built into cryo-EM density maps.

Protein unfolding machinery visualized

9 August 2016|

Using a combined cryo-EM and solution NMR approach the laboratories of John Rubinstein and Lewis Kay have determined the structure and equilibrium distribution of two unique conformers along the ATP hydrolysis cycle of the AAA+ unfoldase VAT. The paper published in PNAS (http://www.pnas.org/content/113/29/E4190.abstract) lends insight into how this class of molecular machines are able to convert the chemical energy of ATP hydrolysis into the mechanical force required […]

An image of an atomic model of a ubiquitinated and dimethylated histone core particle with bound 53BP1 built into a cryo-EM density map.

Seeing the first steps of DNA repair

2 August 2016|

The laboratories of John Rubinstein and Frank Sicheri (Biochemistry), and Dan Durocher (Molecular Genetics) have used electron cryomicroscopy (cryo-EM) to determine the structure of the DNA-damage recognizing protein 53BP1 bound to modified nucleosome core particles. The work, published in Nature (http://www.nature.com/nature/journal/vaop/ncurrent/full/nature18951.html), was led by postdoctoral fellow Marcus Wilson and research associate Samir Benlekbir and provides the first structural insight into how dimethylation and ubiquitination of nucleosomes in […]

An image of missing pieces in the structure of vacuolar type ATPase.

Rubinstein lab found one of the missing puzzle pieces in the structure of the vacuolar type ATPase

1 April 2016|

Vacuolar-type ATPases (V-ATPases) are ATP-powered proton pumps involved in numerous essential processes in the cell. The Rubinstein laboratory has recently used cryo-EM to determine 3D structures of the V-ATPase (Zhao et al. 2015, Nature) and the related mitochondrial ATP synthase (Zhou et al. 2015, eLife). These cryo-EM studies have also demonstrated remarkable conformational heterogeneity in the enzymes. While conformational heterogeneity is biologically interesting, it has limited the ability to get atomic resolution structures […]