News & Events

Events

Understanding Nutrient Uptake by Dominant Members of the Human Gut Microbiota

Date: 
Thursday, March 21, 2019 - 18:30 to 19:30
Speaker: 
Dr. Amy Glenwright - Strynadka Group
Affiliation: 
Centre for Blood Research, University of British Columbia
Event Category: 
CBDG - Chemical Biology Discussion Group
Location: 
Chemistry D215

Abstract:

The human gut contains a dense population of microbes termed the Human Gut Microbiota (HGM) consisting mainly of Bacteroides and Clostridia. Nutrient import by the Bacteroides genus is dictated by the specificity of the transporters and associated enzymes. This process involves a two-component outer membrane complex consisting of a substrate binding protein (SusD-homologue) and a barrel-shaped transport protein (SusC-homologue). These protein classes are widespread in the beneficial Bacteroides species, typically accompanied with degradative enzymes targeting the same substrate, and are thought to be the reason behind the success of these species within the highly complex and competitive HGM. The development of a protocol for native expression and purification of SusCD complexes directly from Bacteroides thetaiotaomicron led to the first atomic resolution x-ray crystal structures of two functionally divergent SusCD complexes. Through this work we demonstrated the SusCD proteins function like a pedal bin with the SusD homologue binding protein acting as the lid on the SusC homologue transporter bin, contrary to the previously suggested mechanism. The SusD homologue lid can open which allows for substrate binding and movement into the SusC homologue barrel for transport into the cell. Furthermore, we obtained structural evidence that SusC is heavily involved in mediating interaction with the substrate through a substrate complex. Fundamentally, this data provided a detailed molecular understanding of how Bacteroides import high molecular weight substrates.