Structural characterization of EXCRT-III assemblies

• Applicant: Professor Dr. Winfried Weissenhorn
• Subject Area: Virology
• Term: from 2005 to 2013
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 13122596

Enveloped viruses such as HIV and Ebola assemble at and pinch off from cellular membranes as newly formed infectious particles. This process is largely mediated by the retroviral polyprotein Gag and the filovirus matrix protein VP40, which contain late domain sequence motifs that help to recruit cellular factors that normally act at endosomal membranes in the sorting of ubiquitylated cargo into vesicles that bud into endosomes giving rise to multi-vesicular bodies. The latter process is morphologically similar to enveloped virus budding and the interference with the protein machinery identified in multivesicular body formation leads to a defect in the pinching off of retroviral particles. Our goal is to understand the structural requirements of a late step in budding, which involves CHMP family protein assembly. We will use X-ray crystallography and biochemical approaches to analyze the structure of central CHMP family members, to study their activation and assembly mechanism, to elucidate their membrane binding properties and to obtain atomic details of their interactions with regulatory partners involved in the budding process.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1175: Dynamics of Cellular Membranes and their Exploitation by Viruses
• International Connection: France