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Research Aims:
TEMIMPS is a collaborative initiative for structure determination of membrane proteins by electron cryo-microscopy (cryo-EM). This approach is well established for producing intermediate and atomic resolution structures and offers the following advantages:
(1) Membrane proteins can be studied within their native lipid environment.
(2) Reduced steric constraints, either within membrane crystals or in isolated, detergent-solubilized complexes, facilitate interactions between membrane proteins and their binding partners, such as ligands and effector proteins.
(3) A 3D map can be produced with poorly ordered, or non-crystalline material, thus providing a template for molecular modeling and characterization of conformational change.

We have assembled a team of investigators with expertise in cryo-EM and specifically in electron crystallography of membrane crystals. As individuals, these investigators have been responsible for innovations in the areas of membrane protein production, biochemistry crystallization, data collection, image processing, and structure determination using methods of cryo-EM.

At TEMIMPS we will focus primarily on determining structures of eukaryotic membrane proteins in their native lipid environment. Our structure determination efforts will include multisubunit membrane proteins and complexes involving soluble binding partners. The majority of our protein targets play a prominent role in human health and disease. These include TRP channels; G-protein coupled receptors, aquaporins, multidrug transporters, intramembrane proteases, and ion pumps.

Another focus of TEMIMPS will be to establish methods to accelerate membrane crystallization screening and data collection, and facilitate high-resolution structure determination. We will build upon recent developments by participating investigators, which include high-throughput membrane crystallization screening, automated imaging by electron microscopy, and automated acquisition of diffraction data from highly ordered membrane crystals. In addition, we will develop novel methods to correct lattice distortions in membrane crystals. The participating investigators have been involved in a large number of software development projects that will serve as joint platform for our collaborative efforts.




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