Membrane-bound proteins play several important roles in biological processes and viral infections make no exception. Especially for enveloped viruses, where the virion-mediated fusion with the target membrane starts the infection cycle and insights about the viral membrane proteins acting as fusion machineries provide targets for drug design. Human cytomegalovirus (HCMV, a member of the enveloped Herpesvirus family) is a widespread highly adapted human pathogen, representing the leading infectious cause of congenital brain defects and a major source of life-threatening complications in transplant recipients and immunodeficient individuals. HCMV is also associated to cancer progression and to the immunosenescence. Licensed drugs for anti-HCMV treatment are characterized by weak activity and high toxicity, and alternative viral targets must be found to develop novel therapeutic strategies. The herpesviral fusion machinery presents an unusal complexity with four up to seven viral proteins involved. A dynamic molecular model of the fusion mechanics is still lacking for HCMV, and a structural description of fusion players is completely absent, thus preventing the rational design of HCMV fusion inhibitors. The present project aims to the structural investigation of HCMV fusion machinery by its in vitro reconstitution with the purified viral players and their crystallisation for structure determination by X-ray diffraction. Molecular biology of the HCMV entry is the current subject of the researcher proponent. The hosting scientist, with a well established espertise in structural studies of membrane proteins and as part of international collaborating networks devoted to foster knowledge and dissemination in the field, will provide the appropriate training environment to develop the researcher interest in the structural virology, a study branch of strong appeal to the european research area for linking basic science and translational research.