X-ray Core Abstract Crystallization is prerequisite for using single crystal X-ray diffraction to derive detailed information on protein structure and interactions at the atomic level. Crystallization of large multi-protein complexes is challenging, and, even if successful, the resulting crystals are usually small and delicate and present multiple challenges including problematic diffraction, which may be low resolution or/and anisotropic. To meet these challenges, a number of new technologies and methodologies for high throughput crystallization, sample cryo-cooling, diffraction quality screening, data collection, and data analysis are necessary to tackle difficult projects. The X- ray core will carry out extensive high-throughput screening to determine the best conditions for crystallizing HIV and/or host factor complexes that are identified by the Interactions Discovery Core and produced by the Protein Core. To obtain crystals of multi-protein complexes of sufficient quality for structural studies, it is often necessary to test a large number of different crystallization conditions and screen numerous crystals to locate even a single specimen that adequately diffracts X-rays. Recent efforts towards improving sample “crystallizability” using techniques such as alanine scanning mutagenesis or the use of chimeric proteins to promote/improve crystal packing has led to structures of highly relevant targets. However, less effort has been spent on visual evaluation and optimization of crystallization. Transmission electron microscopy (TEM) is an ideal approach for this purpose. The PCHPI has implemented the use of TEM as a tool to: 1) discover nanocrystals from crystallization screens and 2) analyze and guide the process of crystallization. Structures will be determined using state-of-the-art post-crystallization handling, data-collection and processing strategies.