Structural biology of clathrin-mediated endocytosis
Clathrin-mediated endocytosis is a fascinating mechanical phenomenon which drives the selective internalisation of molecules into cells. It requires accurate and timely assembly of a clathrin lattice and coordination with a network of more than 20 adaptor proteins to form a coated vesicle which will be able to select molecules from the outside of the cell for delivery to specific destinations. This mechanism acts at many levels within eukaryotic organisms because it supports diverse functions such as nutrient uptake, synaptic vesicle recycling, signalling, determination of cell polarity and development. It is also exploited by viral and bacterial pathogens to gain entry into cells and malfunctions lead to tumour formation, neurodegeneration and heart disease.
We are using high resolution 3D cryo-electron microscopy and dynamic biophysical techniques to understand how the proteins involved in the network of clathrin and its adaptor proteins interact to achieve coated vesicle formation. The superior signal sensitivity of new direct electron detectors has revolutionised the field of structure determination by cryo-electron microscopy, allowing sub-4Å structures of challenging targets such as membrane proteins and ribosomes to be obtained without using X-ray crystallography. We are exploiting this improvement in capability to carry out high resolution structural analysis of clathrin cage complexes.
To find out more about our cryo-electron microscopy facilities visit Advanced Bioimaging Research Technology Platform
Dr Sarah Smith
Current PhD students
Alice Rothnie - Senior Lecturer at Aston University