InstructThe latest webinar in the Instruct-ERIC Structure Meets Function series will be hosted by Instruct UK on 7th June 2022, 11:00 - 12:30 CEST. Register for the webinar here.
Featuring expert speakers from Instruct Centres across Europe, Instruct-ERIC Webinar Series: Structure Meets Function highlights some of the latest developments in structural biology, demonstrating how integrative methods are enabling scientists to decipher the mechanisms that underpin health and disease.
Watch the previous webinars in the series here.
Moderator: Joshua White
Talk 1: Understanding the mechanism of the bifurcating hydrogenase from Thermotoga maritima through the application of cryoEM and symmetry expansion
Speaker: Jamie Blaza, Universiti of York, Uk
Abstract: The electron bifurcating/confurcating [FeFe] hydrogenase from Thermotoga maritima (HydABC) simultaneously oxidises/reduces both NADH and ferredoxin respectively, reducing protons to generate hydrogen and vice versa. The mechanism of bifurcation is of broad interest as it splits an electron pair, passing one electron down-hill and pushing another up-hill, which may have application in synthetic biology circuits. Here, I will present the 2.3 Å structure of HydABC solved by cryoelectron microscopy. Using symmetry expansion we identified two conformations of the C-terminus of HydB. In one conformation the CT of HydB from one HydABC trimer forms a “closed bridge” with the C-terminus of HydA from an adjacent trimer, while in another conformation the C-terminus of HydB is pointing away from the complex (“open bridge”). This bridge is consistent with a gate that stops both electrons travelling down-hill and the results suggest a complicated and unprecedented mechanism of electron bifurcation involving large scale conformational changes. In addition to our scientific findings, this talk will also explain in-depth the classification and symmetry expansion methods we used in the hope that they may be of assistance to other projects.
Talk 2: Structure and mechanism of action of Vip3 toxins
Speaker: Colin Berry, Cardiff University, UK
Abstract: Insects cause major losses to agriculture and are vectors of a range of pathogens. Control using chemical pesticides has led to problems of insect resistance and to concerns over environmental safety (non-target effects) and health concerns. A variety of bacteria produce insecticidal proteins that are potent and highly specific to narrow groups of insects. These have been deployed in the form of sprayed bacteria and in the production of insect-resistant transgenic plants. Vip3 proteins are a family of insecticidal proteins with activity against lepidopteran (butterflies/moths) pests of crops and which
show no sequence homology to any other known proteins. Hence, at the outset of our study, there was no insight into the structure or function of this important new weapon in the fight to control crop loss. Using CryoEM, we have elucidated the structure of the protein in pro- and active forms, demonstrating a major structural rearrangement in the transition to the toxic form. We have identified structural homologies (not detectable at primary sequence level) with other known insecticidal proteins which may give further insight into their mechanisms of action and we have visualised the active toxin at the surface of liposomes during pore formation. We are now able to propose an advanced model of the mechanism of action of the Vip3 proteins; the next step is to use structural techniques to understand insect specificity.
