3D Electron Microscopy Of Molecular Assemblies
Zhang Lab University of Pittsburgh School of Medicine Department of Structural Biology
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Mechanism of Clathrin-mediated Endocytosis
Clathrin-mediated endocytosis is responsible for numerous important cellular functions, such as synaptic vesicle recycling, nutrient uptake, and the regulation of a number of membrane receptors and transporters. Perturbations or disruptions of this process are implicated in much pathology. For example, defective trafficking of glucose transporters to and from the plasma membrane may be a key cause of insulin resistance in Type II Diabetes. While great progress has been made in the identification and characterization of many protein components involved in clathrin-mediated endocytosis, including clathrin, adaptor proteins, dynamin, amphiphysin and other accessory proteins, much less is known about the structural organization of these proteins and their spatial and temporal relationships that are required to understand the molecular mechanism of this process.
clathrin mediated endocytosis
One of our research efforts will be focused on obtaining this essential structural information and determining the architecture of the molecular machinery using molecular cryo-electron microscopy. Several different, yet complementary, approaches of structural analysis by cryo-EM will be employed to study this complex system. These include electron crystallographic studies of two-dimensional or helical protein crystals of individual proteins, single particle approaches to analyze the structures of protein complexes that are not amendable for NMR or crystallographic studies, and electron tomography of macromolecular assemblies and large subcellular structures.

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