Structure and Dynamics of Complexes of G Proteins and their Receptors

16 March 2018|

Ned Van Eps in the Ernst laboratory used DEER spectroscopy together with molecular modeling techniques to map the structure of a complex between a G-protein-coupled receptor (GPCR) and its G protein. A paper describing the methodology used for characterizing the binding interface of the rhodopsin–G protein complex has recently been published in PNAS. The authors discovered that the binding mode of G protein subtypes is distinct and key differences suggest […]

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 ( 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 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 […]

trimer diversity simple phylogenetic shadow

PNAS article on HIV-1 clade C trimers that increase the arsenal of Env immunogens

8 September 2015|

Jean-Philippe Julien at the SickKids Research Institute and collaborators at Scripps report in PNAS two HIV-1 envelope glycoproteins (Env) of clade C sequences that are faithful antigenic and structural mimic of the native trimer in its pre-fusion conformation: the DU422 and ZM197M trimers. A cryo-EM reconstruction of the ZM197M trimer at sub-nanometer resolution revealed important conformational variability in loops that harbor high sequence diversity between HIV-1 clades. HIV-1 clade […]