Structural Biology of Membrane Proteins in Diseases of Aging (360G-Wellcome-203979_Z_16_A)
Solving the 3D molecular structure of membrane proteins has historically been difficult, but recent technological advances have made many more membrane proteins viable targets. Membrane transporters and ion channels are important in all cells, but are particularly important in the nervous system. This project aims to solve a 3D membrane protein structure using either cryo-electron microscopy or x-ray crystallography, beginning with a set of candidate proteins involved in disease or vital function. These include: ABCC5, a Type 2 diabetes associated protein and transporter of the neurotransmitter glutamate in the brain; ABCA7, an Alzheimer’s disease associated protein, which transports lipids; HCN2, an ion channel associated with neuropathic pain and the CNGs, a family of proteins which form heteromeric ion channels found in the retina and olfactory system. We plan to complement the structural study with activity assays of purified protein in combination with known substrates and modulators.
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