University of Dundee

"Structural insight into regulation of enzyme/membrane interactions"

Event Date: 
Thursday, February 27, 2020 - 14:00
Event Location: 
School of Life Sciences, MSI Small Lecture Theatre
Host: 
Dr David Murray
Professor Dario Alessi FRS FRSE FMedSci
Event Speaker: 
Dr Roger Williams FRS FMedSci
Institution: 
MRC Lab of Molecular Biology, Cambridge
Event Type: 
Seminar
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Joint Seminar

 Divisions of Cell & Developmental Biology and MRC Protein Phosphorylation and Ubiquitylation

 

 

 

ALL WELCOME

 
 
Roger Williams is a structural biologist and group leader at the Medical Research Council (MRC) Laboratory of Molecular Biology.  
 
He was educated at Purdue University (BS) and Eastern Washington University (MS). He completed his PhD at the University of California, Riverside in 1986 for research investigating the structure of ribonuclease and is a member of European Molecular Biology Organization and Fellow of the Academy of Medical Sciences. He was awarded the Morton Lectureship by the Biochemical Society in 2008 and was elected a Fellow of the Royal Society in 2017.
 
His group studies the form and flexibility of protein complexes that associate with and modify lipid cell membranes.  His work concerns the biochemistry, structures and dynamics of these key enzyme complexes.
 
Abstract
Members of the phosphatidylinositol 3-kinase (PI3K) family of enzymes evolved from a common ancestor and are present in all eukaryotes, where they have roles in homeostasis and stress response. PI3Ks are lipid kinases whose substrates are components of membranes. They and the protein kinase mTOR regulate response to nutrition and growth factors. Nutrition-sensing pathways are linked through their influence on autophagy and lysosomal sorting, processes that are regulated by the VPS34-PI3K complexes. While the PI3K-related protein kinase mTOR phosphorylates soluble protein substrates, it is activated on lysosomal membranes. Consequently, the activities of these enzymes depend on both their residence time on membranes and the efficiency with which they form the transition state complex once they are bound to membranes. X-ray crystallography provided high-resolution details about the enzyme active sites and helped generate hypotheses regarding membrane interaction. However, more recently, hydrogen/deuterium exchange mass spectrometry (HDX-MS) and electron cryo-microscopy (cryo-EM) have provided a wealth of information regarding mechanisms of regulation of these enzymes. We have applied these approaches to characterise protein/protein interactions, protein/membrane interactions and the conformational changes that accompany these interactions.